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Sodium thiosulfate attenuates liver injury in a rat model of sepsis by modulating ferroptosis and oxidative stress
Inter-regional disparities in emergency department utilization among critically ill patients: A nationwide study from South Korea
Background This study examined inter-regional emergency department (ED) utilization among critically ill patients in South Korea and identified demographic, socioeconomic, and system-level factors. Methods A retrospective analysis of 741,701 critically ill ED visits in 2021 was conducted using the National Emergency Department Information System (NEDIS). Inter-regional utilization was defined as receiving care outside the residential emergency medical service (EMS) region. Patient characteristics were compared between inter- and intra-regional groups. Mixed-effects logistic regression, modified Poisson regression, and average marginal effects (AMEs) were applied to identify associated factors. The results were presented concurrently using odds ratios (ORs), adjusted risk ratios (aRRs), and AMEs, including 95% confidence intervals (CIs). Results Overall, 21.7% of critically ill patients received inter-regional care. Male patients had higher odds of inter-regional utilization (OR 1.08, 95% CI: 1.07–1.10; aRRs 1.05, 95% CI: 1.03–1.08), although their absolute probability was significantly lower (AME –8.29%p, 95% CI: –12.42 to –4.16), reflecting differences between relative and absolute measures. Adults aged 19–44 years (OR 1.35, 95% CI: 1.32–1.39) and 45–64 years (OR 1.24, 95% CI: 1.21–1.27) showed higher odds of inter-regional utilization, although corresponding AMEs were not statistically significant. Among older adults, the 65–74-year group showed a non-significant decrease in absolute probability (AME –0.90%p, 95% CI: –3.39 to 1.58), whereas the 75–84-year group demonstrated a significant reduction (AME –5.78%p, 95% CI: –7.64 to –3.92). Pediatric patients also exhibited elevated odds of inter-regional use. Medical Aid beneficiaries had lower relative odds (OR 0.65, 95% CI: 0.63–0.67), and AMEs showed no statistically significant absolute differences. Inter-hospital transfer (OR 1.20, 95% CI: 1.16–1.24) was associated with higher inter-regional use, with a statistically significant increase in absolute probability (AME + 3.74%p, 95% CI: 0.86–6.63). Arrival by ambulance or private vehicle showed positive but non-significant AMEs. High-acuity patients (KTAS 1–2) and those transferred as their final disposition also demonstrated higher relative odds of inter-regional utilization. Conclusions Inter-regional ED utilization was more likely among men, younger and middle-aged adults, high-acuity patients, and those arriving by ambulance or transferred from another hospital, while Medical Aid patients were less likely to receive such care. These findings highlight the importance of strengthening local emergency capacity, optimizing referral and transfer pathways, and implementing region-specific strategies alongside nationwide initiatives.
A cosmic-ray loaded nascent outflow driven by a massive star cluster
Abstract Cosmic rays are widely held to drive outflows from star-forming galaxies and profoundly influence galaxy evolution. Direct evidence for cosmic-ray carrying outflows is however lacking. At the same time there is increasing awareness of the importance of massive star clusters in the acceleration of cosmic rays in galaxies. Here we report on the discovery of a nascent outflow driven by the massive star cluster Westerlund 1. Giga-electronvolt gamma-ray emission coincident with a cavity visible in atomic hydrogen traces the emergence of a population of relativistic electrons out of the Galactic Disc. The emission is offset from tera-electronvolt gamma-ray radiation surrounding the cluster, but connects to it smoothly spectrally and spatially. The implied energy density of co-accelerated protons and nuclei, assuming standard non-thermal electron/proton injection efficiencies, is at least an order of magnitude higher than that in the general interstellar medium. These particles therefore have the potential to dynamically influence the outflow. This discovery suggests that cosmic-ray loaded outflows may be a common feature of young massive star clusters, with implications for the transport of cosmic rays into the halo of the Galaxy.
Rice farming for climate change adaptation in the Northeastern United States
In response to challenges posed by climate change, rice farming emerges as a strategic adaptation in the agriculture sector in the northeastern United States. Cultivating rice can diversify farming practices, create new sources of income, improve water management, and provide habitats for wildlife, enhancing the sustainability of agricultural systems and rural economies. However, challenges such as methane emissions from rice paddies and the risk of metal(loid) contamination highlight the need for adopting best practices in rice cultivation, particularly in land and water management and the selection of suitable rice varieties. By learning from the experience of other temperate rice farming regions and implementing supportive policies, technology, and cooperative frameworks, farming communities in the northeastern United States can learn to navigate these obstacles, ensuring the successful integration of rice farming into its agricultural landscape.
Comparative assessment of periodontal health among adolescents in Rabat, Morocco using AAP/EFP 2017 and CDC/AAP 2012 classifications
Abstract Periodontal diseases are highly prevalent among adolescents and represent a growing public health challenge worldwide. This study aimed to assess the prevalence and clinical profile of periodontal conditions among Moroccan adolescents and to analyze their association with socio-demographic and behavioral factors. A cross-sectional survey was conducted among 400 students aged 12 to 18 years enrolled in public secondary schools in Rabat, Morocco, using a two-stage cluster sampling method. Periodontal status was evaluated by trained examiners using standardized indices, including probing pocket depth, clinical attachment loss, plaque index, and bleeding on probing. The results revealed that nearly two-thirds of participants presented signs of gingivitis, while a significant proportion exhibited clinical features consistent with periodontitis. Periodontal conditions were more frequent among older adolescents and were associated with poor oral hygiene practices. The findings highlight the early onset and considerable burden of periodontal disease in Moroccan adolescents, underscoring the importance of integrating targeted prevention and early detection strategies into school-based oral health programs. These data provide essential insights for guiding public health policies to improve adolescent oral health and to reduce the long-term impact of periodontal disease in Morocco.
Text cryptography and steganography based on RNA sequences generation, true random number generators, and codebook method
Classic security methods are becoming vulnerable because of technology advancements. The process of combining cryptography and steganography led to overcoming this, where this combination will save the information from potential attackers. This paper proposed a new text security method by combining the cryptography technique and steganography technique, where cryptography is used to encode the message, while steganography is used to hide the ciphertext within an image. The proposed cryptography system has five steps. The first is done by building an RNA sequences generation table to convert the message to RNA sequences, the next step is done by creating a table to convert RNA sequences to decimal numbers. In the third step, the achieved decimal values are converted to binary numbers; after that, used True Random Number Generators method generates the key, and finally, an XOR operation is applied between achieved binary numbers and the generated key. The results achieved by the XOR operation are considered as the ciphertext. Two steps to the proposed steganography method. The first step is done by building a codebook table to select the part of the pixel to store the bit inside it, where the selection part can be either red, green, or blue, and then used a least significant bit to store the bit with no effects on the image. The proposed method presents an efficient solution to secure data, and this method can be applied in different fields, such as information security and privacy protection.
Onset of persistent surface ocean oxygenation during the Great Oxidation Event
Abstract Free oxygen (O 2 ) first began accumulating in Earth’s atmosphere shortly after the Archean-Proterozoic transition during the ‘Great Oxidation Event’ (GOE). The nature of surface ocean oxygenation at this time is, however, poorly quantified, limiting our understanding of planetary oxygenation thresholds. Geochemical records of global ocean redox may potentially shed light on this critical interval. Here, we show that vanadium (V) isotope ratios in 2.32-2.26-billion-year-old (Ga) shales from the Transvaal Supergroup, South Africa, capture a unidirectional transition in global ocean redox conditions shortly above the stratigraphic level marking the canonical rise of atmospheric O 2 . Around 2.32 Ga, sedimentary sinks were dominated by anoxic environments that drove extensive seawater V drawdown. A positive shift in seawater V isotopic composition in the overlying stratigraphy indicates global expansion of marine settings with ≥ 10 μM dissolved O 2 in bottom water, likely restricted to shallow-water environments and attributable to widespread equilibration with an oxygenated atmosphere.
A meta-learning ensemble framework for robust and interpretable prediction of emergency medical services demand
Clinical nurses’ knowledge, attitudes and practices regarding incontinence-associated dermatitis: A cross-sectional study from China
To explore the current status of knowledge, attitudes, and practices (KAP) regarding incontinence-associated dermatitis (IAD) among clinical nurses in China and identify factors influencing these three aspects, this study adopted a cross-sectional design and was conducted in a tertiary hospital in Fujian Province, China, with 1,153 nurses completing the questionnaire. Primary outcome measures included nurses’ IAD-related knowledge, attitude, and practice scores, with scoring rates of 70.6%, 90.9%, and 69.9% respectively; key low-scoring items in knowledge were “IAD care products” (2.04 ± 1.019) and “IAD assessment tools” (2.12 ± 0.923), while low-scoring practice items included “actively participating in IAD seminars” (60%) and “using IAD assessment tools” (66%). Demographic and professional information collected included gender, age, highest educational attainment, work experience, job position, job grade, department, wound/ostomy/incontinence (W/O/I) team membership, and participation in W/O/I care training. Results showed that clinical nurses had insufficient IAD knowledge (only 15.3% with high knowledge levels) and inadequate practices, but held positive attitudes (75.4% with positive attitudes). Notably, male nurses demonstrated more comprehensive IAD knowledge than female nurses (p < 0.05), though no significant gender difference was observed in practice (p = 0.883); this knowledge difference may be associated with male nurses’ more frequent assignment to IAD-high-incidence departments (e.g., ICUs) and higher participation in W/O/I training. Factors influencing nurses’ IAD-KAP included: 1) Common factors across KAP: job position (specialist nurses and head nurses performed better) and W/O/I team membership; 2) Dimension-specific factors: department affiliation (ICU nurses outperformed general ward nurses in knowledge and practice), participation in W/O/I training (improved knowledge and practice), gender (influencing knowledge only), and work experience (longer tenure correlated with more positive attitudes). Highest educational attainment was not a significant influencing factor, possibly due to inconsistent quality of part-time continuing education for nurses. In conclusion, participating nurses exhibited insufficient IAD knowledge and inadequate practices despite positive attitudes, presenting a notable “attitude-practice gap”. Nursing administrators should develop targeted training (e.g., scenario-based training on IAD assessment tools and care products) and encourage female nurses to rotate in high-incidence departments (e.g., ICUs), strengthen resource allocation (e.g., ensuring supply of IAD care products) and promote W/O/I team construction, and optimize continuing education quality to address knowledge disparities, thereby enhancing nurses’ understanding of IAD prevention and improving their related practices.
COVID-19 pandemic and waning immunity disrupted measles population immunity and strategies to close immunity gaps
Effect of HSPA 8 on the biological function of NPC cells and its mechanism
Correction: GATmath and GATLc: Comprehensive benchmarks for evaluating Arabic large language models
Epigenetic regulation of cocaine intake through dopaminergic control of cholinergic interneurons in male mice
Abstract Substance use disorders are chronic neuropsychiatric conditions influenced by multiple factors, shaping individuals’ vulnerability to addictive drugs like cocaine. Here, we reveal that dopamine D2 receptor mediated inhibition of striatal cholinergic interneurons regulates the motivation for cocaine intake by modulating acetylcholine signaling in striatal circuits. This acetylcholine-dependent mechanism contributes to cocaine self-administration through the muscarinic M4 receptor and the histone acetyltransferase Kat5/Tip60. We discover that Kat5 is upregulated in response to cocaine and further show that this leads to acetylation of histone H4 on lysine 8, an epigenetic modification that increases immediate early gene expression and muscarinic M4 receptor in dopamine D1 receptor-expressing medium spiny neurons. Notably, this chain of events is absent in male mice lacking D2 receptor-mediated inhibition of cholinergic interneurons, resulting in reduced cocaine consumption. These findings expand our understanding of how cocaine manipulates striatal circuits to reinforce drug-seeking behavior.
Assessment of mineral adequacy in preprepared raw dog foods labeled as complete
Potential analgesic function of the clitoris in pregnant women: A feasibility study
Currently, the clitoris is considered to exist solely for sexual pleasure. This prospective, single-centre pilot study focuses on and evaluates an alternative function of the clitoris; pain relief during pregnancy and childbirth. Conducted between 2020 and 2023 at Rouen University Hospital, France, this feasibility study challenges the assertion of the singular function of the clitoris. The primary aim was to assess the acceptability of an intervention focusing on the potential analgesic function of the clitoris. The secondary aim was to assess pain relief. Pregnant women were offered the option of self-external massage with a vibrating device (OVD) in the clitoral suspensory ligament area for pain relief. Data were collected via a self-schedule for precise use of the method, including pain assessment before and after the use of the OVD via a self-analytic visual scale. Acceptability was considered to have been achieved if the woman used the OVD at least twice. Comparisons before and after were performed by means of a student’s t-test. With respect to acceptability, among the 32 women included, 26 (81.25%) used an OVD at least twice. Despite concerns about sexual intimacy and the sensitive period of pregnancy, this preliminary feasibility study confirmed the suitability of this mechanical vibration for the majority of the women included. In terms of pain relief, these 26 women used the OVD to manage 304 painful episodes and the feeling of relief was reported in 86.2% of these episodes. Based on a small sample size, the numerical results are obviously highly relative to the disparity of situations and feelings. However, these few consistent reports of a positive analgesic effect encourage further studies into the potential analgesic function of the clitoris.
Early skin seeding regulatory T cells modulate PPARγ-dependent skin pigmentation
Abstract The maintenance of adult tissue homeostasis is dependent on the functional cross-talk between stem cells (SCs) and tissue-resident immune cells. This reciprocal relationship is also essential for tissue organogenesis during early life. The skin harbors a relatively large population of regulatory T cells (Tregs) that accumulate within the first two weeks after birth. A functional role for early skin seeding Tregs (ETregs) during the first week of life is currently unexplored. Here, we show that skin Tregs are detected as early as postnatal day 3 (P3) and enter a dynamic flux of activation marker expression. Punctual ETreg depletion from P6-P8, but not later, resulted in defective hair follicle (HF) melanocyte SC (MeSC) mediated skin pigmentation in juvenile life. Transcriptomic analysis of the whole skin on P9 indicated immediate and pronounced changes in MeSC markers, as well as perturbation of PPARγ target genes in the HF. Accordingly, punctual ETreg depletion, combined with short-term PPARγ antagonization, restored skin pigmentation. Single-cell profiling of P9 skin revealed that PPARγ signalling activity is preferentially diminished in the HF epithelium upon loss of ETregs. Finally, we explored changes in the single-cell transcriptome of the human tissue disorder, vitiligo, characterized by a lack of melanin and consequent skin depigmentation. These analyses showed that the HF cells from lesional vitiligo skin exhibit significant downregulation in PPARγ pathway activation, relative to heathy controls. Overall, ETregs in neonatal skin are critical for sustaining HF PPARγ signaling, which is vital for facilitating MeSC mediated skin pigmentation during postnatal development.
Ubiquitin-specific protease 14 inhibition promotes mitophagy and attenuates neural apoptosis after spinal cord injury
Urinary signatures are associated with calorie restriction-mediated weight loss in obese Diversity Outbred mice
Metabolomic profiles are increasingly being used to identify responders to dietary interventions. Advances using this approach are particularly needed to personalize and enhance the effectiveness of dietary weight loss interventions. Using obese Diversity Outbred (DO) mice that model genetic and phenotypic heterogeneity of human populations, we aimed to identify urinary metabolite signatures associated with responsiveness to calorie restriction (CR)-mediated weight loss. DO mice (150 males, 150 females) were fed a high-fat diet for 12 weeks to induce obesity, then urine was collected and an 8-week CR regimen (30% decrease in energy intake) initiated. At study completion, mice were rank-ordered according to their percent body weight change, with mice in the extreme quartiles deemed CR responders (n = 67) versus nonresponders (n = 67). Targeted semi-quantitative metabolomics identified elevated glutamic acid and hydroxyproline as key urinary metabolites that distinguish CR responders from CR nonresponders, independent of sex. Three urinary metabolites (glutamic acid, hydroxyproline, and putrescine) distinguished male CR responders from nonresponders. Six metabolites (glutamic acid, hydroxyproline, dopamine, histamine, lysine, and spermine) distinguished female CR responders from nonresponders. Multivariate receiver operating characteristic analyses integrated these metabolites to reveal potential sex specific and sex-independent associations of CR-mediated weight loss. Further, pathway analysis identified several metabolic pathways, including arginine and proline metabolism, and alanine, aspartate, and glutamate biosynthesis, that distinguished CR responders from nonresponders and could be indicative of metabolic reprogramming to enhance insulin sensitivity and energy metabolism.
PP-GWAS: Privacy Preserving Multi-Site Genome-wide Association Studies
Abstract Genome-wide association studies help uncover genetic influences on complex traits and diseases. Importantly, multi-site data collaborations enhance the statistical power of these studies but pose challenges due to the sensitivity of genomic data. Existing privacy-preserving approaches to performing multi-site genome-wide association studies rely on computationally expensive cryptographic techniques, which limit applicability. To address this, we present PP-GWAS, a privacy-preserving algorithm that improves efficiency and scalability while maintaining data privacy. Our method leverages randomized encoding within a distributed framework to perform stacked ridge regression on a linear mixed model, enabling robust analysis of quantitative phenotypes. We show experimentally using real-world and synthetic data that our approach achieves twice the computational speed of comparable methods while reducing resource consumption.
Designing AI-generated antimicrobials for targeting bacterial microdomains
Abstract Bacterial membranes are essential for processes such as nutrient transport, signal transduction, and maintaining cellular integrity. Within these membranes, specialized microdomains like cardiolipin-rich domains, serve as key sites for protein localization, membrane curvature regulation, and stress response. These microdomains possess high anionic headgroup density and specific lipid composition, which can enhance electrostatic and hydrophobic interactions with antimicrobial agents. In this study, we investigated whether antimicrobial compounds can selectively target membranes with distinct lateral lipid distributions. To this end, we modeled two bacterial membrane systems: one with a randomized lipid composition and another featuring an idealized cardiolipin-rich microdomain. Using a generative neural network framework guided by specific molecular design criteria, we generated AI-driven antimicrobial candidates and assessed their membrane interactions via free-energy calculations. Our analysis revealed preferential binding of compounds to cardiolipin-rich domains, evidenced by lower binding energies, alongside higher translocation barriers in these regions, attributable to strong electrostatic anchoring and tight lipid packing. Further clustering and feature importance analysis identified recurring structural motifs associated with potent antimicrobial activity, supporting that cardiolipin-rich regions may facilitate selective binding. Parallel toxicity predictions indicated several top candidates have low predicted toxicity, a critical factor for drug development. Notably, the top AI-designed compounds were benchmarked against established membrane-targeting drugs to assess similarities in their antimicrobial activity profiles. By integrating generative AI with advanced membrane modeling, this work establishes a robust framework for the rational design of new membrane-targeting antimicrobials and highlights how membrane composition influences drug-membrane interactions and efficacy.