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Automated extracellular volume fraction measurement for diagnosis and prognostication in patients with light-chain cardiac amyloidosis
Aims T1 mapping on cardiac magnetic resonance (CMR) imaging is useful for diagnosis and prognostication in patients with light-chain cardiac amyloidosis (AL-CA). We conducted this study to evaluate the performance of T1 mapping parameters, derived from artificial intelligence (AI)-automated segmentation, for detection of cardiac amyloidosis (CA) in patients with left ventricular hypertrophy (LVH) and their prognostic values in patients with AL-CA. Methods and results A total of 300 consecutive patients who underwent CMR for differential diagnosis of LVH were analyzed. CA was confirmed in 50 patients (39 with AL-CA and 11 with transthyretin amyloidosis), hypertrophic cardiomyopathy in 198, hypertensive heart disease in 47, and Fabry disease in 5. A semi-automated deep learning algorithm (Myomics-Q) was used for the analysis of the CMR images. The optimal cutoff extracellular volume fraction (ECV) for the differentiation of CA from other etiologies was 33.6% (diagnostic accuracy 85.6%). The automated ECV measurement showed a significant prognostic value for a composite of cardiovascular death and heart failure hospitalization in patients with AL-CA (revised Mayo stage III or IV) (adjusted hazard ratio 4.247 for ECV ≥40%, 95% confidence interval 1.215–14.851, p-value = 0.024). Incorporation of automated ECV measurement into the revised Mayo staging system resulted in better risk stratification (integrated discrimination index 27.9%, p = 0.013; categorical net reclassification index 13.8%, p = 0.007). Conclusions T1 mapping on CMR imaging, derived from AI-automated segmentation, not only allows for improved diagnosis of CA from other etiologies of LVH, but also provides significant prognostic value in patients with AL-CA.
Correction to “Total Syntheses of Scabrolide A and Yonarolide”
Citrus diseases detection using innovative deep learning approach and Hybrid Meta-Heuristic
Citrus farming is one of the major agricultural sectors of Pakistan and currently represents almost 30% of total fruit production, with its highest concentration in Punjab. Although economically important, citrus crops like sweet orange, grapefruit, lemon, and mandarins face various diseases like canker, scab, and black spot, which lower fruit quality and yield. Traditional manual disease diagnosis is not only slow, less accurate, and expensive but also relies heavily on expert intervention. To address these issues, this research examines the implementation of an automated disease classification system using deep learning and optimal feature selection. The system incorporates data augmentation and transfer learning with pre-trained models such as DenseNet-201 and AlexNet to improve diagnostic accuracy, efficiency, and cost-effectiveness. Experimental results on a citrus leaves dataset show an impressive 99.6% classification accuracy. The proposed framework outperforms existing methods, offering a robust and scalable solution for disease detection in citrus farming, contributing to more sustainable agricultural practices.
Biochemical and Computational Characterization of Haloalkane Dehalogenase Variants Designed by Generative AI: Accelerating the S<sub>N</sub>2 Step
Prevalence and risk factors of the most common multimorbidity among Canadian adults
Background The number of persons living with multimorbidity–defined as the co-occurrence of at least two chronic conditions in the same individual–is growing globally, especially in developed countries. Traditionally, this increase has been attributed to a growing aging population, sedentary lifestyle, obesity, low socioeconomic status, and individual genetic susceptibility. Objective To investigate the prevalence and associated risk factors of the most common multimorbidity (MCM) among Canadian middle-aged and older adults. Method Relevant data on all 30,097 middle-aged and older Canadian adults (aged 45 to 85 years) from the Canadian Longitudinal Study on Aging were used for this study. To identify the specific sociodemographic risk factors associated with the MCM, we used survey-specific logistic regression. Findings Overall, co-occurrence of osteoarthritis and hypertension was identified as the MCM among Canadian adults aged 45+ with an estimated prevalence of 16.5%. The results from multivariate analysis showed that seven factors were significantly associated with increased odds of the MCM, which included increasing age, being retired from work (retired vs not retired), poorer rating of perceived health, (very good, good, poor vs excellent), increasing problems with sleep quality (satisfied, dissatisfied vs neutral), and abnormal body-mass index (underweight, overweight, obese vs normal). Also, residents in other urban centres had significantly lower odds than those in urban core. Persons living in Atlantic Canada, Ontario and Quebec were at increased odds of having the MCM compared to those in British Columbia. The odds of the MCM associated with increasing age was significantly higher among Females (OR = 1.12, 95% CI = 1.11–1.13) than Males (OR = 1.08, 95% CI = 1.07–1.10). Conclusion Multimorbidity is a common feature among Canadian adults. The identification of the most prevalent patterns and associated risk factors in this study provides fresh insights into the etiology, progression, and possible prevention of the MCM among Canadian adults.
Highly Photoreactive Semiconducting Polymers with Cascade Intramolecular Singlet Oxygen and Energy Transfer for Cancer-Specific Afterglow Theranostics
Effects of stimuli and contralateral noise levels on auditory cortical potentials recorded in school-age children
Background and objective One of the functions attributed to the auditory efferent system is related to the processing of acoustic stimuli in noise backgrounds. However, clinical implications and the neurophysiological mechanisms of this system are not yet understood, especially on higher regions of the central nervous system. Only a few researchers studied the effects of noise on cortical auditory evoked potentials (CAEP), but the lack of studies in this area and the contradictory results, especially in children, point to the need to investigate different protocols and parameters that could allow the study of top-down activity in humans. For this reason, the aim of this study was to analyze the effect of varying levels of contralateral noise on efferent activity in children by recording CAEPs with tone burst stimuli. Additionally, we aimed at verifying the effects of contralateral noise on cortical processing of speech stimuli. Methods Monaural CAEPs were recorded using tone burst stimuli in quiet and with contralateral white noise at 60 dB and at 70 dB in 65 typically developing school-aged children (experiment 1), and using speech stimuli with contralateral white noise at 60 dB in 41 children (experiment 2). Results In experiment 1, noise induced changes were observed only for P1 and P300 components. P1 latency was prolonged at both noise level conditions, P300 latency was prolonged only in the condition with noise at 70 dB, and P300 amplitude was reduced only in the condition with noise at 60 dB. In experiment 2, noise induced latency delays were observed on P1, P2, N2, and P300 components and amplitude reduction was observed only for N1. Conclusion The effects of noise stimulation were observed on all CAEP components elicited by speech, but the same was not observed in the experiment with tone bursts. The study of noise effects on CAEPs can provide electrophysiological evidence on how difficult listening situations affect sound discrimination and stimulus evaluation at thalamocortical regions.
Dynamic Kinetic Activation of Aziridines Enables Radical-Polar Crossover (4 + 3) Cycloaddition with 1,3-Dienes
Reduction of Cystatin B results in increased cathepsin B activity in disomic but not Trisomy 21 human cellular and mouse models
Down syndrome, resulting from trisomy of human chromosome 21, is a common form of chromosomal disorder that results in intellectual disability and altered risk of several medical conditions. Individuals with Down syndrome have a greatly increased risk of Alzheimer’s disease (DSAD), due to the presence of the APP gene on chromosome 21 that encodes the amyloid-β precursor protein (APP). APP can be processed to generate amyloid-β, which accumulates in plaques in the brains of people who have Alzheimer’s disease and is the upstream trigger of disease. Cathepsin B has potential roles in both APP processing and amyloid-β degradation and has been suggested to contribute to amyloid-β accumulation. An endogenous inhibitor of Cathepsin B, Cystatin B (CSTB), is encoded on chromosome 21. The abundance of this protein is increased in the brains of individuals with DSAD, which may be associated with a decrease in Cathepsin B activity compared to individuals who have Alzheimer’s disease in the general population. Whether targeting CSTB can modulate Cathepsin B activity in the context of trisomy of chromosome 21 is unclear. Here we test if reducing CSTB can alter Cathepsin B activity in a mouse and a cellular model of trisomy of chromosome 21. We find that reducing CSTB abundance increases Cathepsin B activity in disomic controls but not in the presence of trisomy of chromosome 21. These findings offer new insights into the role of CSTB in regulating Cathepsin B activity.
Pseudo-Phosphorylated Tau Forms Paired Helical Filaments in the Presence of High-Curvature Cholesterol-Containing Lipid Membranes
Family support and prayer are invaluable coping strategies for our recovery: Experiences of persons living with cardiovascular diseases
Background It is estimated that 61% of deaths caused by Cardiovascular Diseases (CVDs) globally are attributed to lifestyle-related risk factors including tobacco use, alcohol abuse, poor diet, and inadequate physical activity. Meanwhile, inadequate knowledge and misperceptions about CVDs are disproportionately increasing the prevalence of CVDs in Africa. Moreover, pre-diagnosis awareness/knowledge about CVDs among patients is essential in shaping the extent and scope of education to be provided by healthcare workers. Objective Explore the experiences of patients living with CVDs (PLwCVDs) and accessing care at the Cardiothoracic Centre, Ho Teaching Hospital, regarding their knowledge of CVD-risk factors and coping strategies that work for them. Method We leveraged descriptive phenomenological design to explore the experiences of patients accessing care at the Cardiothoracic Centre at the Ho Teaching Hospital, Ghana. Using the purposive sampling technique, 17 PLwCVDs for 3yrs and above were recruited and included in the study. Thematic analysis was conducted using the qualitative computerised data software, NVivo version 14. Recruitment of participants and general conduct of the study commenced on November 1, 2023 and ended on April 30, 2024. Findings We found that PLwCVDs and accessing care at the Cardiothoracic Centre at Ho Teaching Hospital have adequate pre-diagnosis awareness about CVD-risk factors and their knowledge of same was optimal. Moreover, past unhealthy lifestyles (such as poor dieting, abuse of alcohol, smoking, and inadequate physical activity) may have contributed to participants developing the CVDs. Furthermore, prayers and participation in church activities were the main coping strategies employed by the participants in dealing with CVDs. Conclusion The PLwCVDs and receiving treatment at the Cardiothoracic Centre at the Ho Teaching Hospital are knowledgeable in the CVD-risk factors and adopting positive coping strategies. The Cardiothoracic Centre and government must explore social media facilities to intensify public education and also correct misconceptions about CVDs.
Electrocatalytic Mapping of Metal Fatigue with Persistent Slip Bands
Critique of enhanced power claimed for Quasi-ANCOVA and Dual-Centered ANCOVA
Two related methods, Quasi-ANCOVA and Dual-Centered ANCOVA, have recently been suggested as a way to get greater power when analyzing data from a before and after study. Both methods use group-mean centering where the groups are the treatment and comparison groups. Group-mean centering creates a generated regressor problem. When the estimated standard errors are corrected for the generated regressor problem, there is no longer any gain in power. The corrected Quasi-ANCOVA estimates are identical to those from ANOVA and the corrected Dual-Centered ANCOVA estimates are identical to those from the differences model. These conclusions are derived analytically and also verified using a Monte Carlo simulation.
Dynamic Peptide Nanoframework-Guided Protein Coassembly: Advancing Adhesion Performance with Hierarchical Structures
Geographical patterns of intraspecific genetic diversity reflect the adaptive potential of the coral Pocillopora damicornis species complex
Marine heatwaves are increasing in intensity and frequency however, responses and survival of reef corals vary geographically. Geographical differences in thermal tolerance may be in part a consequence of intraspecific diversity, where high-diversity localities are more likely to support heat-tolerant alleles that promote survival through thermal stress. Here, we assessed geographical patterns of intraspecific genetic diversity in the ubiquitous coral Pocillopora damicornis species complex using 428 sequences of the Internal Transcribed Spacer 2 (ITS2) region across 44 sites in the Pacific and Indian Oceans. We focused on detecting genetic diversity hotspots, wherein some individuals are likely to possess gene variants that tolerate marine heatwaves. A deep-learning, multi-layer neural-network model showed that geographical location played a major role in intraspecific diversity, with mean sea-surface temperature and oceanic regions being the most influential predictor variables differentiating diversity. The highest estimate of intraspecific variation was recorded in French Polynesia and Southeast Asia. The corals on these reefs are more likely than corals elsewhere to harbor alleles with adaptive potential to survive climate change, so managers should prioritize high-diversity regions when forming conservation goals.
Structure–Reactivity Relationship of Zeolite-Confined Rh Catalysts for Hydroformylation of Linear α-Olefins
Vanadate reduction by gram-positive fermentative bacteria isolated from deep-sea sediments on the northern Central Indian Ridge
The oxidation states of vanadium determine its mobility and toxicity, and dissimilatory vanadate reduction has been reported in several microorganisms, highlighting the potential significance of this pathway in the remediation of vanadium contamination and the biogeochemical cycle. However, to date, most known microorganisms capable of reducing vanadate are Gram-negative respiratory bacteria belonging to the phylum Proteobacteria. In this study, we isolated Tepidibacter mesophilus strain VROV1 from deep-sea sediments on the northern Central Indian Ridge and investigated its ability to reduce vanadium and the impact of vanadate on its cellular metabolism. A series of culture experiments revealed that the isolated strain efficiently reduces V(V) to V(IV) during fermentation, even at mM levels, and this reduction involves a direct biological process rather than indirect reduction via metabolic products. Vanadium affects microbial carbon and nitrogen metabolism. Notably, in the presence of vanadate, alanine production decreases, suggesting that metabolic flux is diverted from the transamination reaction to vanadate reduction. T. mesophilus VROV1 is the second Gram-positive bacterium identified to reduce vanadium, following Lactococcus raffinolactis, but these bacteria belong to different classes: T. mesophilus is classified as Clostridia, whereas L. raffinolactis is classified as Bacilli. The specific rate of vanadate removal by VROV1 was as high as 2.8 pmol/cell/day, which is comparable to that of metal-reducing bacteria and markedly exceeds that of L. raffinolactis. Our findings expand the distribution of vanadate-reducing organisms within the bacterial domain. Given the wide range of natural habitats of T. mesophilus and its close relatives, we speculate that fermentative vanadate reduction may have a greater impact on the global biogeochemical cycle of vanadium than previously thought.
Aminoalkylation of Alkenes Enabled by Triple Radical Sorting
Reconstructing prehistoric lifeways using multi-Isotope analyses of human enamel, dentine, and bone from Legaire Sur, Spain
Megalithism has been repetitively tied to specialised herding economies in Iberia, particularly in the mountainous areas of the Basque Country. Legaire Sur, in the uplands of Álava region, is a recently excavated passage tomb (megalithic monument) that held a minimum number of 25 individuals. This study analysed the carbon, nitrogen, oxygen, and strontium isotope ratios of 18 individuals, in a multi-tissue sampling study (successional tooth enamel sampling, incremental dentine sampling, and bulk bone collagen sampling). The results provide a high-resolution reconstruction of individual mobility, weaning, and dietary lifeways of those inhumed at the site. Oxygen and strontium isotope analysis suggest all individuals come from a similar, likely local, geological region, aside from one biological female who presents a notably different geographical birthplace, weaning, and dietary life history than the rest of the burial population. Comparisons to other nearby megalithic sites (∼35km as the crow flies), located in a valley area, reveal that, whilst sharing the same mortuary practices, these individuals held notably different lifeways. They highlight notably earlier ages of cessation of nursing (≤2 years at Legaire Sur vs. ≥4 years in other megalithic tombs), and a greater dependence on pastoralism than previously observed in lowland megalithic graves. The results from Legaire Sur reveal the complexity of the Late Neolithic-Chalcolithic transition in north-central Iberia, categorising yet another separate socio-economic group with distinctive lifeways inhabiting the region.