共找到 20 条结果
Pulmonary hypertension (PH) can be defined as a mean pulmonary artery pressure (mPAP) greater than 20 mm Hg at rest during right heart catheterization (RHC). The reported prevalence of PH throughout the globe has been estimated to impact approximately 1% of the total population, with a majority of those afflicted being women more than men. Numerous etiologies give rise to the pathophysiology of PH, including heart disease (i.e., left-sided heart failure), lung diseases, and other unclear causes related to chronic stages and complications surrounding long-standing pulmonary thromboembolisms, side effects of certain medications, and genetic and environmental factors. Untreated PH can lead to severe morbidities such as cardio-renal syndrome and congestive hepatopathy (cardiac cirrhosis). Management of PH focuses on decreasing pulmonary pressures by using vasodilators such as prostanoids, and phosphodiesterase type 5 (PDE-5) inhibitors, as well as newer treatments such as sotatercept, which inhibits activin signaling, thereby inhibiting excessive cell growth in the pulmonary artery vasculature and down-regulating the pro-proliferative pathways.
Clonal hematopoiesis of indeterminate potential (CHIP) has substantially advanced our understanding of cardiovascular pathogenesis by demonstrating how somatic mutations in hematopoietic stem cells amplify the bone marrow-heart axis to accelerate atherosclerosis and heart failure, building upon the established role of hematopoietic cells in vascular inflammation. Characterized by the age-associated expansion of hematopoietic stem cell clones harboring somatic mutations-most commonly in TET2, DNMT3A, ASXL1, and JAK2-CHIP affects over 10% of individuals older than 70 years and confers a 1.5- to 2-fold increased risk of coronary heart disease and all-cause mortality, independent of traditional cardiovascular risk factors. This review synthesizes current evidence on the epidemiological associations, molecular mechanisms, and therapeutic implications of CHIP in cardiovascular disease. We critically examine how loss-of-function mutations in epigenetic regulators promote a pro-inflammatory macrophage phenotype through NLRP3 inflammasome activation and IL-1β/IL-6 signaling, thereby accelerating atherogenesis, plaque instability, and myocardial fibrosis. Notably, the cardiovascular impact of CHIP exhibits marked gene-specific heterogeneity: TET2 mutations confer the highest risk and demonstrate the greatest responsiveness to anti-inflammatory therapies, whereas DNMT3A mutations show more modest associations and may operate through distinct pathways. The CANTOS trial exploratory analyses and subsequent studies suggest that IL-1β inhibition with canakinumab and colchicine may preferentially benefit TET2-mutant CHIP carriers, suggesting a future of mutation-guided cardiovascular prevention. However, significant knowledge gaps remain, including the lack of prospective, genotype-stratified clinical trials and limited data in non-European populations. We propose that CHIP represents not merely a risk marker but a modifiable therapeutic target, and advocate for the emergence of "Cardio-Hematology" as a new subspecialty bridging hematology and cardiovascular medicine. As the field evolves from discovery to translation, precision approaches targeting specific CHIP genotypes may fundamentally transform cardiovascular risk stratification and treatment.
This study aims to develop and internally validate an AI approach based on a deep learning (DL) algorithm to classify wound photographs as either 'healing well' or 'requiring review' after a total knee arthroplasty (TKA). A prospective cohort study will be conducted at a single, high-volume Elective Orthopaedic Centre. Adult patients who have undergone primary TKAs will be recruited either upon re-attendance at a wound review clinic or if they have a wound concern. Within the first two weeks postoperatively, an orthopaedic research fellow will obtain two standardized photographs of the wound, and the participant will complete a six-item symptom survey. Two blinded consultant orthopaedic surgeons will independently label each case (with the photographic and survey knowledge only) as 'healing well' or 'requires review'. The dataset of wound images will be split into an 80:20 ratio and a pre-trained DL algorithm will be fine-tuned using 80% of the data with five-fold cross-validation being employed. The folds will be generated using stratification not only by outcome labels but also by demographic variables in order to maintain similar distributions across folds. The remaining 20% will be the test set allowing for internal validation and assessment of the efficacy of the developed algorithm. Ethical approval has been granted by the NHS REC/HRA (IRAS 340642). This study will generate one of the first prospectively validated DL tools for orthopaedic wound triage. Embedding objective imaging and symptom data into a DL algorithm will allow for early detection of complications, timely intervention, streamlined follow-up, and support NHS digital-first pathways. This study's design directly mirrors NHS post-TKA pathways, supporting translatability into the current postoperative workflow for patients. The development of an early-detection system further enables patients to communicate concerns and receive timely assessment and treatment of any postoperative wound issues. The findings of this study will be disseminated through peer-reviewed publications and presentations at national and international conferences.
暂无摘要（点击查看详情）
Microarrays have played a pivotal role in the early stages of omics data generation and analysis. For over 15 years, microarray technology dominated the field of transcriptomics, providing high-throughput platforms to measure gene expression levels across thousands of genes simultaneously. Microarrays enabled a wide range of genomic studies, leading to a vast repository of data in public databases such as the Gene Expression Omnibus (GEO). However, with the advent of next-generation sequencing (NGS), the use of microarrays has steadily declined. Despite this, the legacy of microarrays persists, particularly through the wealth of data generated over the years, which continues to fuel genomic research today. This chapter reviews the origins of microarrays and their impact on omics research and discusses the basic principles behind the technology, how it has evolved over the years, and how it lay the groundwork for the field as we know it today.
Artificial intelligence (AI) is increasingly proposed for use in health and health care systems. Beyond technical performance, public perceptions and affective responses influence whether AI technologies are accepted and adopted in real-world contexts. Social media platforms such as X (formerly Twitter) provide large-scale, real-time insight into public discourse surrounding emerging technologies, yet remain underused for examining how health AI is discussed, evaluated, and emotionally framed. This study aimed to develop and apply large language model (LLM)-based methods for exploratory social listening on health AI. This is the first study to map large-scale sentiment, emotional expressions, and confidence-related signals in online discussions of applications of AI to health. We collected 786,750 English-language posts from X (Twitter) published between January 1 and December 5, 2023, using health- and AI-related keywords. We benchmarked an LLM-based annotation framework by using OpenAI's GPT-3.5-Turbo and GPT-4, comparing model classifications with trained human researchers. Annotations included overall sentiment and 6 evaluative domains frequently referenced in the literature surrounding attitudes toward health AI-usefulness, safety, privacy, ethics, quality, and trust. After cleaning, GPT-3.5-Turbo used the best-performing prompts to label 388,009 posts. A subset (n=268,347) was further analyzed using Emollama-7b, an open-source model fine-tuned from Meta's LLaMA2-7B, for emotion detection, and latent Dirichlet allocation for thematic analysis. Comparisons were made across World Health Organization regions. Compared against human annotations, optimized prompts achieved weighted F1-scores above 0.60 across evaluative domains and sentiment classification. Global discourse about health AI was 65.26% (95% CI 65.11%-65.4%) positive and 83.62% (95% CI 83.48%-83.76%) emotionally optimistic, although substantial regional variation was observed in sentiment (P<.001). The Eastern Mediterranean and South-East Asia regions expressed significantly higher levels of positive sentiment and evaluative agreement in the studied features of health AI, alongside frequent discussion of the tech industry and commercial development. In comparison, the Western Pacific region expressed lower confidence and significantly more mentions of research topics (19.27%, 95% CI 18.5%-20.07%). Privacy was the most prominent global concern, with 33.31% (95% CI 32.98%-33.66%) of privacy-related posts expressing perceived risks. In the Region of the Americas, 18.19% (95% CI 17.92%-18.44%) of posts discussed algorithms and data governance, significantly higher than overall. This study offers the first systematic characterization of online health AI discourse at scale, mapping stances toward key features of AI, emotional tone, and discussion topics across regions. LLM-powered social listening is demonstrated as a feasible approach for identifying dominant narratives and regionally distinct concerns, capable of surfacing opinions absent from traditional media. This can extend to studying discourse on other evolving health technologies where public surveying is limited. While methodological refinement and multilingual expansion are needed, this framework can inform timely policy development, risk communication, and responsible health AI governance.
Brain metastases (BM) occur in nearly half of patients with lung cancer and significantly impair survival and quality of life. Historically, limited blood-brain barrier penetration and low intracranial efficacy of systemic therapies restricted treatment options. However, advances in immune checkpoint inhibitors and next-generation CNS-penetrant targeted therapies have reshaped the therapeutic landscape, improving intracranial control and patient outcomes. In parallel, stereotactic radiotherapy has emerged as a precise and effective local treatment with a more favorable safety profile compared with whole-brain radiotherapy. The integration of systemic and local approaches, guided by personalized medicine, offers new opportunities to optimize central nervous system disease control. Nevertheless, these advances raise key challenges regarding treatment sequencing, patient selection, and risk-adapted strategies. This review summarizes the evolving management of lung cancer BM and highlights future directions for clinical trial design, emphasizing the integration of clinical, biological, and radiological tools to guide individualized treatment strategies.
Mercury’s massive metallic core, volatile-rich surface, and extreme space environment establish it as a key end-member in understanding terrestrial planet formation and evolution. With the imminent arrival of the BepiColombo mission, the planet now stands at the threshold of a transformative exploration phase.
Shualim Rockshelter is situated in the arid central highlands of the Negev in southern Israel and features three occupation layers, spanning from the Initial Upper Paleolithic to the Early Upper Paleolithic, with ages ranging from 47 to 36 ka cal. BP. Site chronology was established by radiocarbon dating of ostrich eggshell fragments and optically stimulated dating of sediments. Cultural variability was assessed through a technotypological analysis of each layer, employing the chaîne opératoire methodology. Layers I and II are attributed to the Ahmarian culture, dating roughly from 45 to 36 ka cal. BP, whereas Layer III is associated with the Initial Upper Paleolithic with an age between 46 and 43 ka cal. BP. Intra-site variability indicates technological shifts from unidirectional reduction sequences producing Levallois-like points in Layer III, to bidirectional sequences for the production of coarse el-Wad points in Layer II. Layer I differs from Layer II as it depicts a highly slender point production, based on narrow-fronted unidirectional cores and finely retouched el-Wad points. Layer I also yielded an ostrich eggshell fragment with etchings and an antler point. Two perforated Mediterranean mollusks were found, one in Layer I and the other in Layer II. The various technological modes documented at the site, including the presence of perforated and painted seashells and an antler point, all suggest a large mobility range and sustained intergroup interactions between hunter-gatherers from Mediterranean and arid regions.
The field of regenerative medicine for Parkinson's disease (PD) has reached a pivotal moment. After decades of preclinical research, recent first-in-human clinical trials demonstrated that cell replacement therapy using stem cell-derived dopaminergic neurons is not only feasible and safe but also shows promising signs of efficacy. Here we analyze three landmark 2025 studies, including the phase I/II trial of allogeneic induced pluripotent stem cell-derived dopaminergic progenitors, that mark a significant leap forward for PD therapy. We discuss principles underpinning the therapy, the historical context of fetal tissue transplants, findings from recent trials, and critical challenges. The convergence of robust cell manufacturing, precise stereotactic surgery, and advanced neuroimaging provides compelling evidence that stem cell-based therapies are potentially a viable treatment paradigm for PD.
Host alternation is a common behavioral strategy among many herbivorous insects. The mulberry longhorn beetle, Apriona germari is a destructive wood-boring pest. The adults exhibit rhythmic host alternation between feeding and oviposition hosts. However, the temporal rhythm and regulatory mechanisms underlying this behavior remain unclear. In the present study, by observing the dynamics of the numbers of A. germari on mulberry (Morus alba, feeding host) and willow (Salix babylonica, oviposition host) trees in a cage, we first found that both females and males began to aggregate on mulberry trees at dawn. Following 18:00 at dusk, the number of females on mulberry declined sharply, whereas the number of males decreased slightly, with a greater proportion of males staying on mulberry. To investigate the role of host volatiles in regulating the host alternation in A. germari, we then carried out two-choice olfactory assays to test whether the behavioral responses of A. germari to the host volatiles from mulberry and willow twigs differed between 04:00 and 08:00 (dawn, aggregated on mulberry) and 18:00 to 22:00 (dusk, dispersed from mulberry). Males were consistently attracted to the volatiles from healthy mulberry at both dawn and dusk, but not to those from willow. Females showed no attraction to the volatiles from either of two hosts at dawn; however, at dusk, they were significantly attracted to willow volatiles. Furthermore, volatiles from feeding-damaged mulberry trees were repellent to both sexes, particularly to males at dawn. These results indicate that the rhythmic host alternation in A. germari is partly mediated by host volatiles and an unidentified male-produced pheromone may be present in this species. Our findings can deepen the understanding of the host alternation in longhorn beetles, and offer a theoretical foundation for developing semiochemical-based, eco-friendly strategies for controlling this pest.
Automated CT perfusion (CTP) software is widely used to select patients with large-vessel occlusion stroke for endovascular thrombectomy (EVT), yet treatment thresholds are often applied as if outputs from different platforms are interchangeable. This study compared RAPID and Brainomix CTP outputs in the same thrombectomy cohort. We performed a retrospective observational study of patients with large vessel occlusion who underwent CTP imaging. Paired volumetric data were analyzed using both RAPID and Brainomix algorithms. Inter-platform agreement was assessed using intraclass correlation coefficients (ICC), Pearson correlation (r), and Bland-Altman analysis. A simplified threshold-based reclassification was performed using the volumetric core cutoffs from DEFUSE-3 (<70 mL) and DAWN (<50 mL); this assessed only the volumetric criterion and does not represent full reconstruction of trial eligibility. Our study found 328 EVT patients had complete paired outputs. Median core volumes were 4 mL (RAPID) vs 10 mL (Brainomix); median penumbra volumes 65 mL vs 80 mL. Core agreement was good (r=0.82; ICC=0.81) but showed systematic bias (RAPID - Brainomix: -4.9 mL) with wide 95% limits of agreement (-50.5 to +40.7 mL). Penumbra agreement was lower (r=0.77; ICC=0.74) with larger bias (-19.4 mL) and wide limits (-130.9 to +92.0 mL). Mismatch classification agreed in 91.5% (κ=0.52). Clinically significant core discrepancies occurred in 20.1%. Threshold-based reclassification at the DAWN (<50 mL) and DEFUSE-3 (<70 mL) volumetric cutoffs was discordant in 7.0% and 3.4% of patients, respectively. RAPID and Brainomix correlate overall but are not interchangeable; systematic biases and wide limits of agreement can alter mismatch-based eligibility. Rigid CTP thresholds for EVT selection should be applied cautiously and integrated with broader clinical assessment.
BackgroundRamadan fasting is a significant spiritual practice for Muslims, characterized by the abstention from food and drink from dawn until sunset. The physiological and psychological effects have been extensively researched; however, the impact on emotion regulation difficulties in university students is still inadequately examined.The objectiveThis study was to assess the changes in emotion regulation difficulties experienced by Muslim university students prior to and following the Ramadan fasting period.MethodsA quasi-experimental, within-subject pre-post design was implemented involving 104 full-time fasting students (87.5% female) at a public university in Syria. Participants administered the 16-item Difficulties in Emotion Regulation Scale (DERS-16) alongside a lifestyle questionnaire prior to and following Ramadan. Data were analyzed with Generalized Estimating Equations (GEE) to evaluate changes in DERS total and subscale scores.ResultsIndicate a significant decrease in total DERS scores from pre-to post-Ramadan (M = 44.00 to M = 32.10, p < .001). All five subscales of the Difficulties in Emotion Regulation Scale (DERS) demonstrated significant improvement, encompassing emotional clarity, goal-directed behavior, impulse control, access to emotion regulation strategies, and emotional acceptance. An analysis of lifestyle indicated heightened physical activity and enhanced cognitive functioning, alongside a rise in sleep disturbances.In conclusionEmotion regulation difficulties significantly decreased across the Ramadan period among university students, likely due to a combination of spiritual, behavioral, and physiological factors. The findings endorse the integration of culturally contextualized interventions within university mental health initiatives during Ramadan. Ramadan fasting is an important religious practice observed by Muslims around the world. During Ramadan, people avoid eating and drinking from dawn until sunset. In addition to its spiritual meaning, fasting may also affect mental and emotional well-being. This study explored whether Ramadan fasting was linked to changes in how university students manage their emotions. A total of 104 Muslim university students in Syria completed questionnaires before and after Ramadan. The study measured different aspects of emotional functioning, including emotional awareness, impulse control, ability to stay focused during stress, and access to healthy coping strategies. Students also answered questions about lifestyle habits such as sleep, physical activity, social media use, and concentration. The findings showed that students reported fewer emotional difficulties after Ramadan. Improvements were found in several areas, including emotional clarity, self-control, emotional acceptance, and the ability to manage distress. Students also reported increased physical activity, reduced social media use, and better concentration. However, sleep problems became more common during Ramadan. These findings suggest that Ramadan may provide a supportive environment for emotional growth and self-reflection. Spiritual practices, structured routines, prayer, and community connection may all contribute to these positive emotional changes. Although the study cannot prove that fasting directly caused these improvements, the results highlight the importance of considering cultural and religious practices when supporting student mental health. The study also suggests that universities and mental health professionals may benefit from developing culturally sensitive well-being programs during Ramadan and similar spiritually meaningful periods.
In Greek mythology, Tithonus was the husband of Eos, the goddess of dawn. Granted immortality without the gift of eternal youth, Tithonus became an illustration of senescence without physical or cognitive wellbeing, characterised by not only physical but also cognitive decline - this is one of the earliest literary representations of dementia in Western civilisation. As myths mirror the values and concerns of a society, the depictions of Tithonus across the eras are an interesting window into how the Ancient Greek society dealt with the process of ageing and cognitive decline. In this paper, we discuss what the myth of Tithonus reveals about senescence and its challenges in the classical world. Remarkably, we conclude that many of the contemporary views and burdens of old age and dementia date from Antiquity, suggesting that ageing and its burdens are inherent human concerns, not merely products of the modern context.
Plants synchronize metabolism with the day-night cycle, yet the interplay between circadian rhythms and nitrogen metabolism in leafy vegetables remains unexplored. We profiled spinach (Spinacia oleracea L.) grown under high-nitrogen and low-nitrogen during four diel phases (end of dark, middle of light, end of light, middle of dark), integrating data from RNA-sequencing with measurements of gas exchange, chlorophyll fluorescence, nitrogen forms, amino acids, and enzyme activities. Nitrogen sufficiency enhanced biomass, CO2 assimilation, chlorophyll content, and photosynthetic efficiency, with maxima in the middle of the light phase. Transcriptome analysis revealed that the greatest gene reprogramming occurred at the dark-to-light transition, where the expression of the morning oscillator component LHY peaked and coincided with the accumulation of dawn-biased nitrate-assimilation transcripts (NIA and NiR) and transporters. Peaks enzyme activities lagged transcript peaks by nearly one phase, suggesting transcriptional priming followed by daytime nitrogen assimilation, aligned with photosynthetic energy and carbon skeleton synthesis. Amino acid profiles reflected this coordination, with glutamine elevated during the day and glutamate enriched at night. Nitrogen deficiency suppressed growth, caused accumulation of reactive oxygen species, and activated circadian-regulated DNA repair genes (e.g., MSH2 and RPA2A, indicating genotoxic stress. Together, these findings support a model in which a diel/clock program, amplified by nitrogen sufficiency, gates nitrogen transport and reduction at dawn to couple daytime assimilation with photosynthesis while adjusting oxidative and DNA repair responses. This mechanistic framework clarifies how temporal regulation and nutrient status interact to shape nitrogen use efficiency and stress resilience in leafy vegetables.
Urban zoos are important but complex artificial ecosystems that integrate wildlife conservation with public education. Their soundscapes, including anthrophony, biophony, and geophony, show significant spatiotemporal dynamics. Persistent fluctuations could contribute to chronic stress in captive animals and human visitors, impairing welfare and conservation outcomes. Existing research focuses on static noise levels, neglecting spatiotemporal dynamics in zoo soundscapes. To address this gap, we deployed passive acoustic monitoring (PAM) with 20 acoustic recorders at Zhengzhou Zoo across seven functional zones between weekdays and weekends during summer in 2024. We analyzed six acoustic indices: Acoustic Complexity Index (ACI), Acoustic Diversity Index (ADI), Acoustic Evenness Index (AEI), Bioacoustic Index (BIO), Normalized Difference Soundscape Index (NDSI) and A-weighted sound pressure level (SPL(dBA)). These were combined with non-metric multidimensional scaling, generalized additive models, and kernel principal component analysis. Quantitatively, we found that SPL (dBA) increased by up to 10 dB on weekends compared to weekdays, while ACI rose by approximately 20%. A very strong negative correlation was observed between ADI and AEI, indicating an inverse dynamic between acoustic diversity and evenness. Building on these results, the analysis revealed distinct diel patterns, with biophony dominating during dawn and dusk periods, while anthrophony peaked during day hours. The weekend effect was significantly identified with these elevated SPL (dBA) and ACI, alongside reduced acoustic stability. Significant acoustic divergence was observed among functional zones, with elevated SPL (dBA) and ACI in High-traffic Zone but with reduced BIO in others. The results indicate that biological rhythms, human activities, and environmental structures collectively shape zoo soundscapes, and PAM and acoustic indices can provide a robust scientific basis for acoustic-based animal welfare and visitor management in zoos.
Cognitive abilities may allow flexible responses to variable environments, proving critical to individual survival in many species. When cognitive abilities are associated with survival, we may also expect cognition to be under sexual selection, as mate choice based on cognitive traits can lead to increased fitness. However, evidence for whether and how individuals assess the cognitive abilities of conspecifics is variable and sparse. We investigated whether individual variation in heritable spatial cognitive abilities of food-caching mountain chickadees (Poecile gambeli), which rely on spatial memory for overwinter survival, is associated with differences in song production, a known secondary sexual trait. Males that performed better on a spatial learning task produced higher daily song output than males that performed worse, both throughout the day and at dawn. While males that performed worse on the spatial learning task sang less throughout the day, they allocated more of their total songs to the first hour of the day. Performance on a single reversal learning task was not associated with song output. These results suggest that differences in daily song output may serve as a reliable signal for spatial cognitive abilities in mountain chickadees.
Robusta coffee (Coffea canephora) accounts for about 80% of Uganda's coffee production and supports over 2.2 million livelihoods. Yet recurrent droughts and erratic rainfall, exacerbated by climate change, pose severe threat to its productivity. Despite this threat, Ugandan breeding programs lack drought-tolerant varieties, largely because selection has not incorporated precise physiological traits linked to drought adaptation. Here, we evaluated 165 diverse Ugandan C. canephora genotypes, including local wild accessions, commercial lines, and breeders' selections, under controlled screenhouse drought assay. Morphophysiological traits were collected before, during, and after drought stress. Using linear mixed-effects models, K-means clustering, and the Drought Factor Index, variation in drought tolerance was characterized across genotypes differing in biomass. Drought reduced water relations, gas exchange (gs and E), and PSII efficiency (Fv/Fm, Fo/Fv, ETR, Y(II), and PI) across all biomass groups. Nevertheless, 24 genotypes maintained higher DFI values, stable PSII function (Fv/Fm, PI, Fv/F₀), and less negative pre‑dawn water potential under severe stress. Among all traits, photosynthetic performance index (PI) and Fv/F₀ emerged as the most robust and biologically interpretable predictors of drought tolerance. These fluorescence‑based markers, together with the identified drought‑tolerant genotypes, provide a powerful foundation for accelerating climate‑smart coffee breeding in Uganda.