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Automated characterisation of cerebral microbleeds using their size and spatial distribution on brain MRI
Cerebral microbleeds (CMBs) are small, hypointense hemosiderin deposits in the brain measuring 2–10 mm in diameter. As one of the important biomarkers of small vessel disease, they have been associated with various neurodegenerative and cerebrovascular diseases. Hence, automated detection, and subsequent extraction of clinically useful metrics (e.g., size and spatial distribution) from CMBs are essential for investigating their clinical impact, especially in large-scale studies. While some work has been done for CMB segmentation, extraction of clinically relevant information is not yet explored. Herein, we propose the first automated method to characterise CMBs using their size and spatial distribution, i.e., CMB count in three regions (and their substructures) used in Microbleed Anatomical Rating Scale (MARS): infratentorial, deep, and lobar. Our method uses structural atlases of the brain for determining individual regions. On an intracerebral haemorrhage study dataset, we achieved a mean absolute error of 2.5 mm for size estimation and an overall accuracy > 90% for automated rating. The code and the atlas of MARS regions in Montreal Neurological Institute—MNI space are publicly available. Relevance statement: Our method to automatically characterise cerebral microbleeds (size and location) showed a mean absolute error of 2.5 mm for size estimation and an over 90% accuracy for rating of infratentorial, deep and lobar regions. This is a promising approach to automatically provide clinically relevant cerebral microbleeds metrics. Key Points: We present a method to automatically characterise cerebral microbleeds according to size and location. The method achieved a mean absolute error of 2.5 mm for size estimation. Automated rating for infratentorial, deep, and lobar regions achieved an over 90% overall accuracy. We made the code and atlas of Microbleed Anatomical Rating Scale regions publicly available
A Biomarker Based Peptide Immunoassay for Clostridioides difficile: “Insights from Central India”
Introduction: Clostridioides difficile infection (CDI) is a major healthcare challenge due to its virulence factors, Toxins A and B. Current diagnostic methods like NAAT and EIA face limitations, including overdiagnosis and cultural resistance to stool sample collection, particularly in India. This study explores blood-based diagnostics, focusing on detecting anti-toxin antibodies through advanced proteomics and immunoassays. These innovative approaches aim to improve diagnostic sensitivity, specificity, and patient accessibility, addressing both clinical and cultural barriers. Methods: This prospective observational study was conducted at the Advanced Research Centre of the Central India Institute of Medical Sciences (CIIMS) in Nagpur. The study enrolled 350 patients aged 18–70 years with clinical manifestations of diarrhea. This research focused on methodologies including microbial isolation of Clostridiodes difficile, isolating and analyzing novel proteins through LC-MS/MS, designing and synthesizing antigenic peptides, and standardizing peptide ELISA. Results: The study successfully isolated and analyzed toxins A and B from C. difficile. The toxins were visualized using a 10% SDS-PAGE gel matrix, followed by peptide design and analysis. The developed immunoassay was tested on 350 serum samples, revealing a higher prevalence of toxin A than toxin B in the central Indian population. Conclusions: The peptide-based immunoassay developed in this study marks a notable improvement in diagnosing Clostridioides difficile infection, especially in contexts where stool sample testing is impractical or culturally sensitive. Offering rapid, sensitive, and patient-friendly detection of anti-toxin antibodies, this method shows potential for enhancing CDI management and controlling its spread. However, additional refinement and validation are necessary to confirm its standalone diagnostic utility. The findings also underscore the intricate relationship between bacterial virulence, host immunity, and clinical outcomes, opening avenues for personalized treatments
A systematic evaluation of sorption-based thermochemical energy storage for building applications: Material development, reactor design, and system integration
Sorption-based thermochemical energy storage (TCES) has attracted substantial attention due to its remarkable potential for long-term and high-capacity heat storage. The efficacy of a TCES system hinges on the seamless integration and coordinated operation of its components. For instance, the choice of thermochemical materials can exert a profound influence on the system's heat storage capacity and stability. Meanwhile, the design of the reactor, along with other critical system components, such as condensers and evaporators, can significantly affect the reaction kinetics of the sorption material, as well as the system's achievable temperature lift and thermal power output. This review paper conducts a comprehensive evaluation of TCES technologies for building applications. It delves deep into three pivotal aspects: material development, reactor design, and system integration, with the aim of elucidating the synergistic relationships among these components. In the aspect of material development, it meticulously reviews the characteristics and system-scale performance of diverse sorption materials. These include physical adsorbents, mono-salt composites, mixed-salt composites, and encapsulated salts. Regarding reactor design, it explores the heat storage potential of various reactor configurations, such as packed bed, moving bed, fluidized bed, modular design, and those integrated with air channels or grain-coated heat exchangers. In terms of system integration, it investigates the effective ways in which TCES systems can be incorporated into building energy systems, such as solar heating systems, air conditioning units, and building envelopes. Through this systematic evaluation, the study endeavors to provide a detailed understanding of the current state-of-the-art and challenges in TCES for building applications, and moreover, to offer insights and directions for future research and development in this field to enhance the energy efficiency and sustainability of buildings
Impact of caprock complexity on carbon dioxide plume behaviour and storage security in the Bunter Sandstone Formation
Carbon capture and storage (CCS) is expected to play a vital role in achieving greenhouse gas reduction targets. The lower Triassic Bunter Sandstone Formation in the UK Southern North Sea is considered one of the most promising CO2 storage sites. The Bunter Sandstone reservoir is structurally complex, featuring shale inter-layers, fractures, and, in particular, vertical and horizontal variations in the structure of overlying caprocks within the potential storage zone. This study demonstrated the need to include all of this complexity in a model of a ‘Bunter-like’ storage site.Due to the lack of detailed geological information on Bunter, four different plausible scenarios (Cases 1–4) were developed to evaluate the impact of CO2 storage on the integrity of the complex caprock structure. The study simulated the injection of 34.2 million tons of supercritical CO2 at a rate of 0.683 million tons per year over 50 years, followed by a 950-year shut-in period (no injection) to monitor the long-term behaviour and migration of the injected CO2.The study findings indicate that the use of an oversimplified caprock model, which assumed only a single impermeable caprock layer and no CO2 leakage, would give rise to misleading conclusions about CO2 plume migration. When comparing CO2 plume migration between scenarios with either a multi-layered, variegated caprock, versus just a single caprock, it was found that 20 % of the injected CO2 leaked in the former, while no leakage was observed through the latter. Further, the presence of a chimney-like structure, within a multi-layered caprock, facilitated lateral CO2 plume movement due to advection forces, unlike with a single, uniform caprock.In a scenario with both shale inter-layers in the reservoir and a chimney in the caprock, while, during the post-injection period, fracture re-activation was observed in the upper inter-layer near the chimney zone in both multi-layer and single caprocks, this occurred significantly earlier for the former compared to the latter. The presence of a chimney in the caprock led to significant localised downward CO2-rich brine fingering in the reservoir below, caused by gravitational instability and heterogeneity in petrophysical properties, due to leakage through the chimney.Calcite minerals significantly influenced caprock porosity across all Cases studied, while halite changes within sub-layers varied between multi-layer and single caprocks. Over the 1000-year simulation period, most of the injected CO2 remained in the supercritical phase, followed by dissolved CO2, hysteresis trapping, and finally, mineralisation. The long-term spreading behaviour of the leaked fraction of the plume is very different for multi-layer, as opposed to single, caprocks.This study demonstrated the importance of intricate feedback interactions, occurring in systems with complex seal and reservoir geologies, for controlling the overall plume migration behaviour
Outcomes of patient and public involvement in the development of the Cognitive Decline after Brain Radiosurgery (CoDe B-Rad) study: refining the research question and methodology
Objectives Patient and public involvement (PPI) was sought in the development of the protocol for the Cognitive Decline after Brain Radiosurgery (CoDe B-Rad) study, which aims to identify potential side effects of stereotactic radiosurgery (SRS). PPI served to refine the research question and methodology.Design PPI.Setting PPI conducted online with people based in the UK. The CoDe B-Rad study is running in regional National Health Service tertiary care in the UK and is currently nearing recruitment completion.Participants Patients and carers with lived experiences of brain radiotherapy. Contributors were identified through national charities.Procedures Initial focus groups were planned, but participation proved challenging. Instead, online questionnaires, one-to-one discussions and participation in support groups were completed.Results All contributors experienced changes to their cognition and/or quality of life (QoL) after radiotherapy. Quantifying the side effects of SRS and minimising them were identified as a research gap. Discussion group participation proved challenging. PPI plans were altered to accommodate the physical and mental needs of contributors. It was decided to combine the Montreal Cognitive Assessment along with European Organisation for Research and Treatment in Cancer QLQ-C30 and BN20 to capture cognitive status and QoL of patients with brain metastases and meningiomas after SRS. Patients/carers recommended for sessions to be restricted to 30 min and testing to be offered face-to-face, online, in hospital or at patients’ homes. Coproduction was not achievable with our patient population but that did not diminish the input of contributors nor the impact it had on designing the study protocol.Conclusions In cancer research, diligent considerations are required to ensure the suitability of involvement methods for this vulnerable population. Flexibility and adaptability of draft PPI plans are essential to achieve meaningful contributions. The protocol of the ongoing CoDe B-Rad study was positively shaped by people with lived experiences of brain radiotherapy.Trial registration number NCT06466720 (CoDe B-Rad study)
Personalization variables in digital mental health interventions for depression and anxiety in adolescents and youth: a scoping review
Introduction: The impact of personalization on user engagement and adherence in digital mental health interventions (DMHIs) has been widely explored. However, there is a lack of clarity regarding the prevalence of its application, as well as the dimensions and mechanisms of personalization within DMHIs for adolescents and youth.Methods: To understand how personalization has been applied in DMHIs for adolescents and young people, a scoping review was conducted. Empirical studies on DMHIs for adolescents and youth with depression and anxiety, published between 2013 and July 2024, were extracted from PubMed and Scopus. A total of 67 studies were included in the review. Additionally, we expanded an existing personalization framework, which originally classified personalization into four dimensions (content, order, guidance, and communication) and four mechanisms (user choice, provider choice, rulebased, and machine learning), by incorporating non-therapeutic elements. Results: The adapted framework includes therapeutic and non-therapeutic content, order, guidance, therapeutic and non-therapeutic communication, interfaces (customization of non-therapeutic visual or interactive components), and interactivity (personalization of user preferences), while retaining the original mechanisms. Half of the interventions studied used only one personalization dimension (51%), and more than two-thirds used only one personalization mechanism. This review found that personalization of therapeutic content (51% of the interventions) and interfaces (25%) were favored. User choice was the most prevalent personalization mechanism, present in 60% of interventions. Additionally, machine learning mechanisms were employed in a substantial number of cases (30%), but there were no instances of generative artificial intelligence (AI) among the included studies.Discussion: The findings of the review suggest that although personalization elements of the interventions are reported in the articles, their impact on younger people’s experience with DMHIs and adherence to mental health protocols is not thoroughly addressed. Future interventions may benefit from incorporating generative AI, while adhering to standard clinical research practices, to further personalize user experiences
Selection Increases Mitonuclear DNA Discordance but Reconciles Incompatibility in African Cattle
Mitochondrial function relies on the coordinated interactions between genes in the mitochondrial DNA and nuclear genomes. Imperfect interactions following mitonuclear incompatibility may lead to reduced fitness. Mitochondrial DNA introgressions across species and populations are common and well documented. Various strategies may be expected to reconcile mitonuclear incompatibility in hybrids or admixed individuals. African admixed cattle (Bos taurus × B. indicus) show sex-biased admixture, with taurine (B. taurus) mitochondrial DNA and a nuclear genome predominantly of humped zebu (B. indicus). Here, we leveraged local ancestry inference approaches to identify the ancestry and distribution patterns of nuclear functional genes associated with the mitochondrial oxidative phosphorylation process in the genomes of African admixed cattle. We show that most of the nuclear genes involved in mitonuclear interactions are under selection and of humped zebu ancestry. Variations in mitochondrial DNA copy number may have contributed to the recovery of optimal mitochondrial function following admixture with the regulation of gene expression, alleviating or nullifying mitochondrial dysfunction. Interestingly, some nuclear mitochondrial genes with enrichment in taurine ancestry may have originated from ancient African aurochs (B. primigenius africanus) introgression. They may have contributed to the local adaptation of African cattle to pathogen burdens. Our study provides further support and new evidence showing that the successful settlement of cattle across the continent was a complex mechanism involving adaptive introgression, mitochondrial DNA copy number variation, regulation of gene expression, and selection of ancestral mitochondria-related genes
Atlas-Based Templates vs. Subject-Specific Tractography: Resolving the Debate
The first annual International Society of Tractography (IST) debate in Corsica in 2024 explored key challenges and controversies in tractography. This article examines the debate sparked by the provocative statement, "Tractography cannot give us anything we can't get from an atlas template." This debate contrasted two approaches: (1) white matter atlas templates, which provide standardized, population-based brain representations useful for studying brain structure and performing group comparisons, and (2) subject-specific tractography, which reconstructs individual brain connections using diffusion MRI, enabling in vivo "virtual dissection" of white matter pathways. We introduce key concepts, present arguments for and against the statement, and, as advocates of tractography, highlight its value while acknowledging the strengths of both approaches
The impact of uncertainty estimation on radiomic segmentation reproducibility and scan–rescan repeatability in kidney MRI
Background: Radiomics holds great potential but is hindered by segmentation and scan-rescan variability, which affect the reproducibility and repeatability of radiomic analysis, respectively. Recently, deep learning (DL) has shown promise in improv- ing segmentation accuracy, thereby enhancing radiomic stability. Moreover, including uncertainty quantification into DL models could provide confidence assessments for segmentations, ultimately improving the trustworthiness and robustness of radiomic outputs.Purpose: This study investigated whether the reproducibility and repeatability of radiomic features, in relation to segmentation and scan-rescan variability, respec- tively, could be enhanced by extracting features exclusively from confidently seg- mented regions, rather than from regions defined without accounting for uncertainty- related information. Additionally, this study assessed whether stable features derived from uncertainty-aware segmentation could improve the classification of healthy versus pathological sub jects.Methods: A publicly available kidney MRI dataset, including subjects with chronic kidney disease (CKD) and healthy controls (HC), was used to assess the robustness of the segmentation methods across diverse clinical scenarios. A deterministic U-Net model was first implemented to generate kidney masks without considering segmen- tation uncertainty. Then, Monte Carlo dropout (MCD) and test-time augmentation (TTA) were applied to address uncertainty in DL-based segmentation. Both methods were trained using the traditional Dice loss and a recently proposed Dice Plus loss to improve model calibration. Confidence level-based masks were defined from the predictions with uncertainty, identifying kidney regions segmented with different levels of certainty. Radiomic features were extracted from ground truth masks, deterministic masks, and confidence level-based masks. These features were grouped into four classes based on their intraclass correlation coefficient values in relation to both segmentation and scan-rescan variability. Finally, based on the identified stable features, a classification model was developed for each approach to distinguish between CKD and HC subjects.Results: The accuracy results were comparable across all the implemented models, with Dice score coefficients consistently above or near 0.9. Most radiomic features were unstable with respect to both segmentation and scan-rescan variability when uncertainty information was not considered. However, including uncertainty increased the number of features repeatable with respect to scan-rescan variability in both CKD and HC subjects. The greatest improvement was observed with the MCD approach trained with the Dice Plus loss, whereby the number of repeatable features increased from 24 to 70 out of 105 in total, for both CKD and HC subjects. Improvements in reproducibility with respect to segmentation variability were not consistent across methods and subjects groups. Regarding the classification analysis, all uncertainty-based approaches performed comparable to the reference one using ROC curves.Conclusions: Integrating uncertainty quantification into DL-based segmentation for radiomic features extraction represents a promising approach to enhance the robustness of radiomic analysis against segmentation and scan-rescan variability, as well as its ability in distinguishing pathological from healthy subjects. Additionally, such integration improves the reliability and interpretability of radiomic analysis, contributing to more informed clinical decision-making
An organic solvent-free route for preparing silica-alkoxylated polyethyleneimine adsorbents for CO2 capture
Mesoporous silica-supported polyethyleneimine (PEI) and, more recently, alkoxylated PEI (APEI) are promising adsorbents for CO2 capture, displaying high adsorption capacity and selectivity. Wet impregnation is the established synthesis procedure for preparing silica-PEI. However, excessive quantities of organic solvents, particularly methanol, have invariably been used for both PEI alkoxylation and polymer mixing with silica. This study demonstrates an organic solvent-free synthesis method for 1) mesoporous silica preparation from sodium silicate solution, 2) PEI alkoxylation, and 3) the subsequent impregnation of silica-PEI using minimal water, typically with a water-to-silica mass ratio not exceeding 1.0. For large scale samples (up to 5 kg) preparation, controlled drying is essential to retain approximately 5 Wt.% moisture, preserving CO2 capture performance. APEIs can be tailored for direct air capture (30 °C) and industrial processes (50 °C) by controlling the alkoxylation chemistry and degree. Silica-APEI exhibits enhanced oxidative stability and reduced moisture co-adsorption, which extend operational lifespan and lower regeneration energy consumption. This water-based synthesis eliminates the need for excess organic solvents, such as methanol, preventing volatile organic compound (VOC) emissions, reducing drying energy consumption, and enhancing sustainability, making large-scale production commercially viable