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Traumatic brain injury (TBI) is one of the commonest presentations to emergency departments and is associated with seizures carrying different significance at different stages following injury. We describe the epidemiology of early and late seizures following TBI, the significance of intracranial haemorrhage of different types in the risk of later epilepsy and the gaps in current understanding of risk factors contributing to the risk of post-traumatic epilepsy (PTE). The delay from injury to epilepsy presents an opportunity to understand the mechanisms underlying changes in the brain and how they may reveal potential targets for anti-epileptogenic therapy. We review existing treatments, both medical and surgical and conclude that current research is not tailored to differentiate between PTE and other forms of focal epilepsy. Finally, we review the increasing understanding of the frequency and significance of dissociative seizures following mild TBI.

Educational data mining is capable of producing useful data-driven applications (e.g., early warning systems in schools or the prediction of students’ academic achievement) based on predictive models. However, the class imbalance problem in educational datasets could hamper the accuracy of predictive models as many of these models are designed on the assumption that the predicted class is balanced. Although previous studies proposed several methods to deal with the imbalanced class problem, most of them focused on the technical details of how to improve each technique, while only a few focused on the application aspect, especially for the application of data with different imbalance ratios. In this study, we compared several sampling techniques to handle the different ratios of the class imbalance problem (i.e., moderately or extremely imbalanced classifications) using the High School Longitudinal Study of 2009 dataset. For our comparison, we used random oversampling (ROS), random undersampling (RUS), and the combination of the synthetic minority oversampling technique for nominal and continuous (SMOTE-NC) and RUS as a hybrid resampling technique. We used the Random Forest as our classification algorithm to evaluate the results of each sampling technique. Our results show that random oversampling for moderately imbalanced data and hybrid resampling for extremely imbalanced data seem to work best. The implications for educational data mining applications and suggestions for future research are discussed.

miR-21 is a 22-nucleotide long microRNA that matches target mRNAs in a complementary base pairing fashion and regulates gene expression by repressing or degrading target mRNAs. miR-21 is involved in various cardiomyopathies, including heart failure, dilated cardiomyopathy, myocardial infarction, and diabetic cardiomyopathy. Expression levels of miR-21 notably change in both heart and circulation and provide cardiac protection after heart injury. In the meantime, miR-21 also tightly links to cardiac dysfunctions such as cardiac hypertrophy and fibrosis. This review focuses on the miR-21 expression pattern and its functions in diseased-heart and further discusses the feasibility of miR-21 as a biomarker and therapeutic target in cardiomyopathies.

ObjectivesCroup is a common emergency presentation for children under 3.1 Croup can often be successfully treated in the community, but occasionally requires admission or intensive care. Scoring systems including the Westley and modified Taussig Scores can help risk stratify and determine the correct treatment algorithm. Local, national and international guidelines differ in their drugs, dosing and escalation recommendations. This study aims to evaluate the diagnosis, treatment and re-attendance rates of children presenting to the emergency department (ED) of a tertiary hospital with croup.MethodsRetrospective service evaluation involving 246 children presenting to paediatric ED over a winter season (01/09/21–28/02/22). Electronic notes from patient’s ED attendance were analysed for: date and time of attendance, scoring, vitals, dose, frequency and formulation of drugs, intensive care escalation and re-presentation.ResultsThe mean age of presentation was 37 months and 72% of patients were male. Only 14.2% of patients had scoring used (15 used Westley, 11 used modified Taussig and 10 had unspecified scores). Of clinicians who did use scoring, 63% were ED doctors and 37% paediatricians. There was a significant correlation between severity of croup score, number of steroids used (p=0.000641) and dose given (p=0.0194). 88% of children were given steroids, usually initiated by ED nurses, meaning doctor review occurred after treatment initiation.The average time between 1st and 2nd, and 2nd and 3rd doses was 45 and 143 minutes respectively. Overall 2.8% re-presented with croup later, with an average time between discharge and re-attendance of 40 hours. This had no significant correlation with the dose of steroid used.ConclusionScoring systems enable risk stratification, selection of appropriate treatment algorithms, and timely escalation, and also have medicolegal implications. The sparse use of scoring, especially in paediatric compared to ED doctors, may reflect differences in awareness, training approaches or documentation style. The majority, but not all, clinicians gave 150mcg/kg dexamethasone regardless of croup severity, in line with literature showing no benefit in higher steroid doses.2Patients also received additional dexamethasone after 45 minutes despite literature showing that maximal effect is only seen at 2 hours.3 Consistent practice will reduce unnecessary steroid administration and additional cost. This evaluation highlights the need for more frequent scoring of croup and closer cohesion between local and national guidelines, which may improve a unified approach among clinicians.ReferencesCroup DW. Johnson, 2016.CM Parker, et al. Predinisolone versus dexamethasone for croup: a randomised controlled trial, 2015.A Gates. et al. Glucocorticoids for croup in children, 2022.

Enlarged or irregularly shaped nuclei are frequently observed in tissue cells undergoing senescence. However, it remained unclear whether this peculiar morphology is a cause or a consequence of senescence and how informative it is in distinguishing between proliferative and senescent cells. Recent research reveals that nuclear morphology can act as a predictive biomarker of senescence, suggesting an active role for the nucleus in driving senescence phenotypes. By employing deep learning algorithms to analyze nuclear morphology, accurate classification of cells as proliferative or senescent is achievable across various cell types and species both in vitro and in vivo. This quantitative imaging‐based approach can be employed to establish links between senescence burden and clinical data, aiding in the understanding of age‐related diseases, as well as assisting in disease prognosis and treatment response. Nuclear morphology (size and shape) is a quantifiable marker of senescence. Deep learning algorithms, detecting and measuring nuclear morphology, consistently classify senescent and proliferating cells across various cell types and species, holding clinical potential. Experimental manipulation of nuclear size can trigger a senescence (‐like) state, confirming the predictive power of nuclear morphology. A causal link between nuclear morphology and senescence warrants further research.

Background Sarcopenia is an age-related condition characterized by the progressive decline of skeletal muscle mass and function. Although adiponectin is known for its anti-inflammatory and insulin-sensitizing effects that support muscle regeneration, paradoxically, elevated levels in older adults are linked to decreased muscle mass, strength, and performance. This study aimed to investigate the relationship between adiponectin levels, age, body composition, and functional status in elderly individuals, as well as to perform in vitro analyses of adiponectin resistance. Methods A cohort of 393 elderly subjects underwent anthropometric, bioimpedance, and functional assessments. Plasma adiponectin levels were measured by ELISA, and AdipoR1/AdipoR2 expression in peripheral blood mononuclear cells (PBMCs) was evaluated. In vitro, human skeletal muscle cells (SkMCs) were exposed to high concentrations (50 µM) of AdipoRon, a dual AdipoR1/AdipoR2 agonist, for 24 and 72 h. Analyses include cell viability, oxidative stress, protein homeostasis, autophagy, proteasome activity, and lipid metabolism. Results In elderly subjects, plasma adiponectin levels negatively correlated with BMI ( r =  -0.129; p  = 0.03), lean mass ( r =  -0.252; p  = 0.001), muscle mass ( r =  -0.296; p  = 0.001), and physical performance (SPPB score; r =  -0.163; p  = 0.007). After adjusting for BMI and fat mass, adiponectin levels positively correlated with age ( r  = 0.281; p  = 0.001). AdipoR2 expression in peripheral blood mononuclear cells was inversely associated with both age and adiponectin levels, suggesting adiponectin resistance in aging. In vitro, high dose of AdipoR agonist -AdipoRon exposure leads to oxidative stress, impaired proteostasis, dysregulated lipid metabolism, AdipoR2 receptor downregulation, and reduced cell viability. Together, these findings support a model in which elevated adiponectin in aging reflects adiponectin resistance and cellular stress rather than beneficial adiponectin signaling, contributing to muscle dysfunction. Conclusions These findings highlight a shift in adiponectin signaling during aging, with the downregulation of AdipoR2 promoting systemic adiponectin resistance. Excessive AMPK activity, in the context of impaired AdipoR2 function, contributes to redox imbalance and metabolic dysfunction in the skeletal muscle, favoring a “senescent-like” phenotype. Graphical Abstract

Some of the most important issues surrounding unconventional oil and gas (UOG) extraction are the possible impacts of this activity on potable groundwater resources and how to minimise and mitigate such impacts. A groundwater vulnerability map for UOG extraction has been developed as part of an interactive vulnerability map for South Africa in an effort to address such concerns and minimize possible future impacts linked to UOG extraction. This article describes the development of the groundwater theme of the interactive vulnerability map and highlights important aspects that were considered during the development of this map, which would also be of concern to other countries that may plan to embark on UOG extraction. The policy implications of the groundwater vulnerability map for managing UOG extraction impacts is also highlighted in this article.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths and obesity is a known risk factor for its development and poor prognosis. Adipose tissue (AT) actively contributes to CRC progression and cachexia. Here, we investigated molecular crosstalk between tumor cells and different visceral AT depots (normal, intra- and peri-tumoral), focusing on metabolic and (epi)genetic alterations. Using WGS analysis, we explored VAT role in CRC progression, demonstrating how its proximity to the tumor impacts metabolic and phenotypic changes. Intra-VAT (within 5 cm of lesion), closest to the tumor, underwent significant metabolic remodeling, characterized by upregulation of markers of the white-brown AT transition (UCP-1, TMEM26), lipid metabolism (PON3) and a reduction in adipocyte turnover (Pref-1, adiponectin). Peri-VAT (within 15 cm) and HVAT (over 15 cm) exhibited progressively fewer alterations, suggesting a gradient effect of tumor on surrounding AT. Intra-VAT displayed increased fibrosis (TGF-β, collagen) and cachexia-related markers (IL-8), and mutations in key oncogenes (KRAS, HLA, MET), highlighting a direct interaction between tumor cells and AT driving CRC progression. Mutations in genes such as KRAS, HLA, and PIK3CA were shared between CRC and its Intra-VAT, indicating potential biomarkers for tumor progression and immune evasion. miRNA analysis revealed upregulation of miR-21 and miR-92a in Intra-VAT, with circulating miR-92a correlating with increased body fat and decreased lean mass in CRC patients, suggesting their involvement in both local metabolic remodeling and systemic changes. Altered PON3 DNA methylation patterns were also observed, correlating with metabolic parameters. Our findings underscore AT’s critical role in the CRC microenvironment as an active player in CRC progression and cachexia. Metabolic and genetic alterations decreased in VAT with increasing distance from the tumor. Intra-VAT may serve as a critical therapeutic target and biomarker for CRC progression, impacting surgical and postoperative strategies. Future studies should focus on targeting tumor-adipose crosstalk to improve treatment outcomes, including experimental validation of the identified genetic alterations and investigation of their functional roles in tumor progression and immune evasion.

Bacterial binding to platelets is a key step in the development of infective endocarditis (IE). Sialic acid, a common terminal carbohydrate on host glycans, is the major receptor for streptococci on platelets. So far, all defined interactions between streptococci and sialic acid on platelets are mediated by serine-rich repeat proteins (SRRPs). However, we identified Streptococcus oralis subsp. oralis IE-isolates that bind sialic acid but lack SRRPs. In addition to binding sialic acid, some SRRP - isolates also bind the cryptic receptor β-1,4-linked galactose through a yet unknown mechanism. Using comparative genomics, we identified a novel sialic acid-binding adhesin, here named AsaA ( a ssociated with s ialic acid a dhesion A), present in IE-isolates lacking SRRPs. We demonstrated that S . oralis subsp. oralis AsaA is required for binding to platelets in a sialic acid-dependent manner. AsaA comprises a non-repeat region (NRR), consisting of a FIVAR/CBM and two Siglec-like and Unique domains, followed by 31 DUF1542 domains. When recombinantly expressed, Siglec-like and Unique domains competitively inhibited binding of S . oralis subsp. oralis and directly interacted with sialic acid on platelets. We further demonstrated that AsaA impacts the pathogenesis of S . oralis subsp. oralis in a rabbit model of IE. Additionally, we found AsaA orthologues in other IE-causing species and demonstrated that the NRR of AsaA from Gemella haemolysans blocked binding of S . oralis subsp. oralis , suggesting that AsaA contributes to the pathogenesis of multiple IE-causing species. Finally, our findings provide evidence that sialic acid is a key factor for bacterial-platelets interactions in a broader range of species than previously appreciated, highlighting its potential as a therapeutic target.

Aim We investigated Quaternary range dynamics of two closely related but ecologically divergent species (cold-tolerant Edraianthus serpyllifolius and thermophilic Edraianthus tenuifolius) with overlapping distribution ranges endemic to the western Balkan Peninsula, an important yet understudied Pleistocene refugium. Our aims were: to test predictions of the ‘refugia-within-refugia' model of strong genetic subdivisions due to population isolation in separate refugia; to explore whether two ecologically divergent species reacted differently to Pleistocene climatic fluctuations; and to test predictions of the displacement refugia model of stronger differentiation among populations in the thermophilic E. tenuifolius compared with the cold-tolerant E. serpyllifolius. Location The western Balkan Peninsula. Methods We gathered amplified fragment-length polymorphism (AFLP) data and plastid DNA sequences from two to five individuals from 10 populations of E. serpyllifolius and 22 populations of E. tenuifolius, spanning their entire respective distribution areas. AFLP data were analysed using a Bayesian clustering approach and a distance-based network approach. Plastid sequences were used to depict relationships among haplotypes in a statistical parsimony network, and to obtain age estimates in a Bayesian framework. Results In E. serpyllifolius, both AFLP and plastid sequence data showed clear geographic structure. Western populations showed high AFLP diversity and a high number of rare fragments. In E. tenuifolius, both markers congruently identified a major phylogeographic split along the lower Neretva valley in central Dalmatia. The most distinct and earliest diverging chloroplast DNA (cpDNA) haplotypes were found further south in the south-easternmost populations. North-western populations, identified as a separate cluster by Bayesian clustering, were characterized by low genetic diversity and a low number of rare AFLP markers. Main conclusions Clear evidence for multiple Pleistocene refugia is found not only in the high-elevation E. serpyllifolius, but also in the lowland E. tenuifolius, despite the lack of obvious dispersal barriers, in line with the refugia-within-refugia model. Genealogical relationships and genetic diversity patterns support the hypothesis that cold-adapted E. serpyllifolius responded to climatic oscillations mostly by elevational range shifts, whereas thermophilic E. tenuifolius did so mainly by latitudinal range shifts, with different phases (and probably extents) of range expansion. In contrast to the displacement refugia hypothesis, the two elevationally differentiated species do not differ in their genetic diversity.