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Abstract A knowledge of the complex phenomena that regulate T1 signal on Magnetic Resonance Imaging is essential in clinical practice for a more effective characterization of pathological processes. The authors review the physical basis of T1 Relaxation Time and the fundamental aspects of physics and chemistry that can influence this parameter. The main substances (water, fat, macromolecules, methemoglobin, melanin, Gadolinium, calcium) that influence T1 and the different MRI acquisition techniques that can be applied to enhance their presence in diagnostic images are then evaluated. An extensive case illustration of the different phenomena and techniques in the areas of CNS, abdomino-pelvic, and osteoarticular pathology is also proposed. Critical relevance statement T1 relaxation time is strongly influenced by numerous factors related to tissue characteristics and the presence in the context of the lesions of some specific substances. An examination of these phenomena with extensive MRI exemplification is reported. Key Points The purpose of the paper is to illustrate the chemical-physical basis of T1 Relaxation Time. MRI methods in accordance with the various clinical indications are listed. Several examples of clinical application in abdominopelvic and CNS pathology are reported. Graphical Abstract

Abstract Background A manual toothbrush is an indispensable tool for promoting and maintaining oral health worldwide but given the non-biodegradable and non-recyclable thermoplastic materials from which it is made, it cannot be considered free of threats to the environment. Therefore, also in light of the World Dental Federation's goals to implement and initiate policies for sustainable dentistry, this study evaluates the sustainability of two materials most used for manual toothbrush bristles, namely nylon, and silicone. Objectives The objective is to investigate the optimal solution to reduce the environmental impact of toothbrushes, and how the environmental impact would change if only the brush head was changed instead of the entire toothbrush. Methods Life Cycle Assessment and Carbon Footprint were used. Four manual toothbrushes with nylon bristles, and a handle in polypropylene with/without silicone parts (N1, N2, N3, N4) and two manual toothbrushes, with silicone bristles, but one with polypropylene handle only (Si1), the other with polypropylene handle and silicone parts (Si2) were evaluated. Results A toothbrush with silicone bristles is more sustainable than one with nylon bristles in all 18 impact categories, with average values of − 14%. In addition, eliminating only the brush head instead of the entire toothbrush could result in savings of 4.69 × 10‒3 kg CO2 eq per toothbrush. Therefore, based on the results of this study and to meet Dentistry's need to reduce its environmental impact, the ideal toothbrush should be lightweight, with less superfluous material, and with less impactful materials such as silicone instead of nylon. Conclusions The concluding indications for improving the sustainability of toothbrushes are therefore: (i) eliminate the amount of superfluous material; (ii) develop lighter models; and (iii) develop models in which only the brush head is replaced rather than the entire toothbrush.

Abstract Background Humic acid affects plant growth. Its source and structure may play a central role to its functionality. The relationship between humic acid and plant bioactivity is still unclear. This study investigated the biostimulation effects of two natural humic acids derived from soil (SHA) and lignite (LHA) on Lepidium sativum in comparison to a synthetic humic acid model (HALP) with known structure. Results All humic acids positively affected cress seed germination and root elongation. Greater root hairs density and dry matter, compared to control, were observed using concentration of 5 mg L−1 for HALP, 50 mg L−1 for LHA, and 100 mg L−1 for SHA. The germination index was the largest (698% more effective than control) with 50 mg L−1 of SHA, while it was 528% for LHA, and 493% for HALP at 5 mg L−1. SHA contained the lowest aromatic and phenolic C content, the largest pK2 value of 9.0 (7.7 for LHA and 7.6 for HALP), the least ratio between the aromaticity index and lignin ratio (ARM/LigR) of 0.15 (0.66 for LHA and 129.92 for HALP), and at pH 6.3 the lowest amount of free radicals with a value of 0.567 × 1017 spin g−1 (1.670 × 1017 and 1.780 × 1017 spin g−1 for LHA and HALP, respectively), with the greatest g value of 2.0039 (2.0035 for LHA and 2.0037 for HALP). Conclusions The overall chemical structure of humic acids exerted a biostimulation of cress plantlets. The level of the intrinsic stable free radicals identified by EPR in the humic acids resulted well correlated to the ARM/LigR ratio calculated by NMR. Our results suggested that HA biostimulation effect is related to its applied concentration, which is limited by its free radical content. The modulation of the humic supramolecular structure by ROS and organic acids in root exudates can determine the release of bioactive humic molecules. When the content of the intrinsic humic free radicals is high, possible molecular coupling of the bioactive humic molecules may hinder their biostimulation activity. In such cases, a low humic acid concentration appears to be required to achieve the optimum biostimulation effects. Graphical Abstract

Abstract E3 ubiquitin protein ligase encoded by ARIH2 gene catalyses the ubiquitination of target proteins and plays a crucial role in posttranslational modifications across various cellular processes. As prior documented, mutations in genes involved in the ubiquitination process are often associated with autism spectrum disorder (ASD) and/or intellectual disability (ID). In the current study, a de novo heterozygous mutation was identified in the splicing intronic region adjacent to the last exon of the ARIH2 gene using whole exome sequencing (WES). We hypothesize that this mutation, found in an ASD/ID patient, disrupts the protein Ariadne domain which is involved in the autoinhibition of ARIH2 enzyme. Predictive analyses elucidated the implications of the novel mutation in the splicing process and confirmed its autosomal dominant inheritance model. Nevertheless, we cannot exclude the possibility that other genetic factors, undetectable by WES, such as mutations in non-coding regions and polygenic risk in inter-allelic complementation, may contribute to the patient's phenotype. This work aims to suggest potential relationship between the detected mutation in ARIH2 gene and both ASD and ID, even though functional studies combined with new sequencing approaches will be necessary to validate this hypothesis.

Community pharmacy practice in Indonesia has shifted to a patient-centered model, offering a range of services that include treatment advice, chronic disease management, and public health promotion. This shift benefits consumers who visit community pharmacies as their initial healthcare point. The Indonesian healthcare system, a mix of public and private providers, is governed by a decentralized structure, fostering significant investment in private healthcare despite access limitations due to financial capacity. Medicines distribution, managed by the District Health Office, ensures supply to primary healthcare facilities, with community pharmacies regulated by the Ministry of Health and the Indonesian National Food and Drug Agency. Despite stringent regulations mandating comprehensive services, most pharmacists are not remunerated for their services. Pharmacy staff, including formally qualified pharmacists and pharmacy technicians, are registered professionals, with recent trends indicating a shift towards employing pharmacy technicians to enable pharmacists to focus on clinical roles. Economic factors and innovative service delivery modes, such as telepharmacy and online purchasing, are expected to influence future practices, enhancing the pharmacist's role in chronic disease management and other health conditions. The evolving community pharmacy practice in Indonesia reflects broader changes in the healthcare system and professional roles, with continued progression anticipated.

SRY-box transcription factor (SOX) genes, a recently discovered gene family, play crucial roles in the regulation of neuronal stem cell proliferation and glial differentiation during nervous system development and neurogenesis. Whole exome sequencing (WES) in patients presenting with generalized epilepsy, intellectual disability, and childhood emotional behavioral disorder, uncovered a de novo variation within SOX12 gene. Notably, this gene has never been associated with neurodevelopmental disorders. No variants in known genes linked with the patient’s symptoms have been detected by the WES Trio analysis. To date, any MIM phenotype number associated with intellectual developmental disorder has not been assigned for SOX12. In contrast, both SOX4 and SOX11 genes within the same C group (SoxC) of the Sox gene family have been associated with neurodevelopmental disorders. The variant identified in the patient here described was situated within the critical high-mobility group (HMG) functional site of the SOX12 protein. This domain, in the Sox protein family, is essential for DNA binding and bending, as well as being responsible for transcriptional activation or repression during the early stages of gene expression. Sequence alignment within SoxC (SOX12, SOX4 and SOX11) revealed a high conservation rate of the HMG region. The in silico predictive analysis described this novel variant as likely pathogenic. Furthermore, the mutated protein structure predictions unveiled notable changes with potential deleterious effects on the protein structure. The aim of this study is to establish a correlation between the SOX12 gene and the symptoms diagnosed in the patient.

Abstract Human learning varies greatly among individuals and is related to the microstructure of major white matter tracts in several learning domains, yet the impact of the existing microstructure of white matter tracts on future learning outcomes remains unclear. We employed a machine-learning model selection framework to evaluate whether existing microstructure might predict individual differences in learning a sensorimotor task, and further, if the mapping between tract microstructure and learning was selective for learning outcomes. We used diffusion tractography to measure the mean fractional anisotropy (FA) of white matter tracts in 60 adult participants who then practiced drawing a set of 40 unfamiliar symbols repeatedly using a digital writing tablet. We measured drawing learning as the slope of draw duration over the practice session and measured visual recognition learning for the symbols using an old/new 2-AFC task. Results demonstrated that tract microstructure selectively predicted learning outcomes, with left hemisphere pArc and SLF3 tracts predicting drawing learning and the left hemisphere MDLFspl predicting visual recognition learning. These results were replicated using repeat, held-out data and supported with complementary analyses. Results suggest that individual differences in the microstructure of human white matter tracts may be selectively related to future learning outcomes.

Abstract Laser-driven dynamic compression experiments of plastic materials have found surprisingly fast formation of nanodiamonds (ND) via X-ray probing. This mechanism is relevant for planetary models, but could also open efficient synthesis routes for tailored NDs. We investigate the release mechanics of compressed NDs by molecular dynamics simulation of the isotropic expansion of finite size diamond from different P-T states. Analysing the structural integrity along different release paths via molecular dynamic simulations, we found substantial disintegration rates upon shock release, increasing with the on-Hugnoiot shock temperature. We also find that recrystallization can occur after the expansion and hence during the release, depending on subsequent cooling mechanisms. Our study suggests higher ND recovery rates from off-Hugoniot states, e.g., via double-shocks, due to faster cooling. Laser-driven shock compression experiments of polyethylene terephthalate (PET) samples with in situ X-ray probing at the simulated conditions found diamond signal that persists up to 11 ns after breakout. In the diffraction pattern, we observed peak shifts, which we attribute to thermal expansion of the NDs and thus a total release of pressure, which indicates the stability of the released NDs.

Abstract The increasing pervasiveness of ICT technologies and sensor infrastructures is enabling police departments to gather and store increasing volumes of spatio-temporal crime data. This offers the opportunity to apply data analytics methodologies to extract useful crime predictive models, which can effectively detect spatial and temporal patterns of crime events, and can support police departments in implementing more effective strategies for crime prevention. The detection of crime hotspots from geo-referenced data is a crucial aspect of discovering effective predictive models and implementing efficient crime prevention decisions. In particular, since metropolitan cities are heavily characterized by variable spatial densities of crime events, multi-density clustering seems to be more effective than classic techniques for discovering crime hotspots. This paper presents the design and implementation of MD-CrimePredictor (Multi- Density Crime Predictor), an approach based on multi-density crime hotspots and regressive models to automatically detect high-risk crime areas in urban environments, and to reliably forecast crime trends in each area. The algorithm result is a spatio-temporal crime forecasting model, composed of a set of multi-density crime hotspots, their densities and a set of associated crime predictors, each one representing a predictive model to forecast the number of crimes that are estimated to happen in its specific hotspot. The experimental evaluation of the proposed approach has been performed by analyzing a large area of Chicago, involving more than two million crime events (over a period of 19 years). This evaluation shows that the proposed approach, based on multi-density clustering and regressive models, achieves good accuracy in spatial and temporal crime forecasting over rolling prediction horizons. It also presents a comparative analysis between SARIMA and LSTM models, showing higher accuracy of the first method with respect to the second one.

Abstract In vitro models of pediatric brain tumors (pBT) are instrumental for better understanding the mechanisms contributing to oncogenesis and testing new therapies; thus, ideally, they should recapitulate the original tumor. We applied DNA methylation (DNAm) and copy number variation (CNV) profiling to characterize 241 pBT samples, including 155 tumors and 86 pBT-derived cell cultures, considering serum vs serum-free conditions, late vs early passages, and dimensionality (2D vs 3D cultures). We performed a t-SNE classification and identified differentially methylated regions in tumors compared to cell models. Early cell cultures recapitulate the original tumor, but serum media and 2D culturing were demonstrated to significantly contribute to the divergence of DNAm profiles from the parental ones. All divergent cells clustered together acquiring a common deregulated epigenetic signature suggesting a shared selective pressure. We identified a set of hypomethylated genes shared among unfaithful cells converging on response to growth factors and migration pathways, such as signaling cascade activation, tissue organization, and cellular migration. In conclusion, DNAm and CNV are informative tools that should be used to assess the recapitulation of pBT-cells from parental tumors.

IntroductionVaccination practice is a well-known individual protective measure for biological risk in healthcare. During the COVID-19 pandemic vaccine hesitancy has grown among healthcare workers (HCWs). The study aims to investigate how vaccine hesitancy influences the psychological burden experienced by healthcare workers.MethodsThis study aimed to explore attitudes of HCWs in acceptance or refusal of vaccinations related to the risk of psychological impairment (PI) and describe the associated occupational factors, during the seasonal flu/COVID-19 vaccination campaign of 2022–2023. 302 HCWs were enrolled in the study. A questionnaire was self-administered, including two scales on the risk of psychological impairment (Psychological Injury Risk Indicator, PIRI) and vaccine hesitancy (Adult Vaccine Hesitancy Scale, AVHS).ResultsPIRI scores revealed that 29.8% of participants were at risk of PI. Differences in sex, age, occupational seniority, professional category, and night shifts were found between HCWs at risk of PI and those not at risk. Females registered a four-fold higher risk than males (85.6% vs. 14.4%, χ2 = 4.450, p

Arteriovenous malformation of the brain (bAVM) is a vascular phenotype related to brain defective angiogenesis. Involved vessels show impaired expression of vascular differentiation markers resulting in the arteriolar to venule direct shunt. In order to clarify aberrant gene expression occurring in bAVM, here we describe results obtained by methylome analysis performed on endothelial cells (ECs) isolated from bAVM specimens, compared to human cerebral microvascular ECs. Results were validated by quantitative methylation-specific PCR and quantitative realtime-PCR. Differential methylation events occur in genes already linked to bAVM onset, as RBPJ and KRAS. However, among differentially methylated genes, we identified EPHB1 and several other loci involved in EC adhesion as well as in EC/vascular smooth muscle cell (VSMC) crosstalk, suggesting that only endothelial dysfunction might not be sufficient to trigger the bAVM phenotype. Moreover, aberrant methylation pattern was reported for many lncRNA genes targeting transcription factors expressed during neurovascular development. Among these, the YBX1 that was recently shown to target the arteridin coding gene. Finally, in addition to the conventional CpG methylation, we further considered the role of impaired CHG methylation, mainly occurring in brain at embryo stage. We showed as differentially CHG methylated genes are clustered in pathways related to EC homeostasis, as well as to VSMC-EC crosstalk, suggesting as impairment of this interaction plays a prominent role in loss of vascular differentiation, in bAVM phenotype.

Recuperando algumas discussões sobre a performance docente de Gilles Deleuze, presentes em certa literatura francófona recente, esse ensaio apresenta algumas correlações dessa performatividade docente deleuziana com elementos da filosofia do autor. Para tanto, apresenta-se um breve panorama da discussão presente em uma leva de comentadores, articulando-as com discussões conceituais presentes no corpus deleuziano e deleuzo-guattariano. Como hipótese norteadora, defende-se haver em Deleuze uma preocupação em filosofar a partir de um lastro sensível mais do que racional, sendo impossível compreender sua prática docente sem levar em consideração seu apelo por uma sensibilidade filosófica.

Abstract Age‐appropriate breastfeeding and introduction to complementary foods can shape child feeding practices, ensure adequate energy and nutrient intake and prevent linear growth faltering. This study aimed to assess mothers' and health workers' knowledge of timely introduction to complementary foods and evaluate the relationship between delays in complementary feeding and subsequent linear growth. We conducted two rounds of surveys (March/August 2017) among 249 health workers (n = 249) and caregivers (n = 2635) of children 6–23 months of age. We collected information about socio‐demographic characteristics, knowledge and practice related to timely introduction to complementary foods. The study was conducted in households from the Productive Safety Net Programme (PSNP) districts, in four highland regions of Ethiopia. Delays in the introduction to complementary feeding were widespread with 53% of children 6–8 months of age not consuming solid, semisolid or soft foods in the past 24 h. After controlling for child, caregiver and household characteristics, children not introduced to complementary foods by 6–8 months had a 0.48 SD lower length‐for‐age z‐score at 12–15 months. Caregivers' knowledge was strongly and inversely correlated with untimely introduction of complementary foods in logistic regressions (OR = 0.55, p

Abstract Child undernutrition disproportionally affects children in low‐ and middle‐income countries. In Ethiopia, both wasting and stunting are serious public health concerns, with high human and economic costs. Understanding the dynamics in ponderal and linear growth faltering is critical to inform the design of innovative interventions that can prevent both wasting and stunting in poor and complex settings. Using two longitudinal studies conducted in 2017 and 2019 in four highland regions of Ethiopia, we evaluated the dynamics and drivers of child growth faltering in children 6–23 months of age (N = 5003). Child wasting prevalence peaked during the first 6 months of life, whereas stunting increased significantly after 6 months of age. Male sex, child illnesses (i.e., diarrhoea or fever) and low consumption of fruits and vegetables were associated with higher odds of acute undernutrition (P