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Uncovering key biomarkers, potential therapeutic targets and development of deep learning model in heart failure

Heart failure (HF) represents a significant public health concern, characterized by elevated rates of mortality and morbidity. Recent advancements in gene sequencing technologies have led to the identification of numerous genes associated with heart failure. By utilizing available gene expression data from the Gene Expression Omnibus (GEO) database, we conducted a screening for differentially expressed genes (DEGs) related to heart failure. Key genes were identified through intersection analysis in conjunction with weighted gene co-expression network analysis (WGCNA). Following this, we pinpointed four essential genes (ITIH5, ISLR, ASPN, and FNDC1) by employing functional enrichment analyses, machine learning approaches, protein-protein interaction (PPI) assessments, gene set enrichment analysis (GSEA), and immune infiltration evaluations. Additionally, a novel diagnostic model for heart failure was successfully developed using a deep learning convolutional neural network (CNN), and its diagnostic performance was validated within public datasets. Analysis via single-cell RNA sequencing further indicated stable up-regulation patterns of these genes across various cardiomyocyte types in HF patients. Moreover, the exploration of drug-protein interactions revealed two potential therapeutic drugs targeting the identified key genes, with molecular docking offering a feasible pathway for this connection. In conclusion, we identified four potential key biomarkers closely related to HF and two possibly effective small molecules, which provide significant insights into the molecular mechanisms underlying heart failure and the search for new therapeutic targets.

Entropy-Regulated Selective Synthesis of Cyclic Polymers and Polycatenanes by Lewis Pair Polymerization

Fracture fixation in the hand and wrist: A 16-year population-based study of 56 163 patients from the Swedish National Patient Register

Hand and wrist fractures are among the most common orthopaedic injuries, with a growing trend toward surgical treatment. However, large-scale data on regional variations and treatment trends remain limited. This population-based study analyses the incidence, trends, and regional variations in hand and wrist fracture fixation with plates and screws in Sweden from 2008 to 2023, with predictive modelling for future trends. A total of 56,163 patients aged ≥15 years underwent fixation (code NDJ69). Southern regions, including Skåne and Halland, had the highest fixation rates (>100/100,000), while northern areas like Norrbotten had significantly lower rates (<20/100,000). Women ≥65 years had the highest incidence. Predictive models indicate a continued increase in procedures, particularly among women aged ≥65, through 2035. These findings highlight regional disparities and the ongoing shift towards surgical treatment in older populations, emphasizing the need for optimized treatment strategies to ensure equitable access to care.

Late-Stage Aromatic C–H Bond Functionalization for Cysteine/Selenocysteine Bioconjugation

Understanding Anomalous Cage-Escape Dynamics in Photoredox Processes Driven by a Fe(III) N-Heterocyclic Carbene Complex

Developing a high-quality patient-centric integrated model for emergency care system in selected districts of India: An implementation research protocol (INDIA-EMS Study)

Introduction Integrated emergency care systems are essential for achieving universal health coverage and managing time-sensitive conditions. In India, emergency care remains fragmented, with limited resources and coordination across healthcare tiers. The INDIA-EMS study aims to develop and evaluate a patient-centric, high-quality integrated emergency care model in diverse Indian districts. Methodology The proposed implementation research is designed as a mixed methods study to be conducted over a 3-year period in selected districts of the states of Punjab, Gujarat, Madhya Pradesh, Odisha and Puducherry. The public/private medical college hospital/ tertiary care hospital in the district will serve as a hub and primary health care services as spokes. The health facilities will be graded according to the availability of resources for their readiness and preparedness to provide care for handling a particular emergency condition. The steps to build and implement the model are: 1. a gap analysis related to emergency care at both pre-hospital and health facility level; 2. a community-based survey in a sample of 30,000 in 5 districts for EMD burden estimates and health-seeking behaviour at baseline and endline; 3. use a consolidated framework for implementation research to develop, optimise and implement hub and spoke model through three cycles of iterative processes; and; 4.evaluation for feasibility, acceptability, cost, effectiveness and coverage. Discussion A high-quality patient-centric integrated emergency care model may be able to ensure efficient delivery of care to patients experiencing time-sensitive emergencies and advance towards the coveted target under Sustainable Development Goals (SDGs). Ethics and dissemination Ethics approval was obtained in all the project sites. The results of the project will be submitted to a peer-reviewed journal for publication, in addition to national and state-level dissemination. Trial registration The trial is registered with CTRI (Clinical Trial Registry of India; CTRI/2024/01/061304).

Highly Porous, Electrically Conductive Two-Dimensional Nickel–Hexaaminodehydrobenzoannulene Frameworks

Medical associations’ guidance on caring for patients experiencing incarceration in the United States

The United States has one of the highest incarceration rates in the world. Carceral status can complicate clinical encounters in community and academic settings for an already medically vulnerable population. While it is likely physicians will encounter patients experiencing incarceration in their practice, there are few educational opportunities dedicated to ensuring delivery of healthcare that protects patient dignity, autonomy, and privacy. Professional medical associations can play a role in filling this physician knowledge gap. The goal of this analysis is to catalogue and analyze the current landscape of official medical association documents addressing healthcare of people experiencing incarceration. A systematic Internet search was conducted of American Medical Association House of Delegates associations and their existing documents. Out of 116 associations included in the systematic search, 16 groups published materials on incarceration. From these 16 associations, 44 documents were identified and coded thematically. Documents served four main purposes: education on incarceration (28/44), clinical guidance (25/44), logistical guidance (27/44), and policy advocacy (30/44). Common topics included medical conditions of people experiencing incarceration, patient factors antecedent to incarceration, and specialty or population-specific information. Few medical associations have published material on incarceration and the paucity of pragmatic clinical guidance was particularly pronounced. A lack of resources from medical associations can lead to variability and lapses in best healthcare practices when treating patients experiencing incarceration. Medical associations should consider developing guidance for clinicians to maximize this patient population’s autonomy and dignity.

Magneto-optical Effect of Dark State in 0D Metal Halides through HT/FC Vibrational Coupling

Investigating the use of a one-page infographic to improve recruitment and retention to the BASIL+ randomised controlled trial: A Study Within a Trial (SWAT)

Background Low participant recruitment and retention rates are a significant barrier to successful Randomised Controlled Trials (RCTs). A Study Within A Trial (SWAT) is an effective way to explore which trial delivery methods may be useful for improving participant recruitment and retention rates. Infographics are a useful information delivery tool that may improve participants’ understanding of the trial and thus improve recruitment or retention rates. This SWAT was embedded within the Behavioural Activation in Social Isolation (BASIL+) RCT. BASIL+ was delivered during the Covid-19 pandemic and evaluated the clinical and cost-effectiveness of a brief psychological intervention (Behavioural Activation) to mitigate depression and loneliness in older adults with multiple long-term health conditions. Methods Twelve research sites were randomly allocated 1:1 to either the SWAT intervention group (participant information included a one-page infographic) or the SWAT control group (participant information did not include a one-page infographic). The primary outcome was the recruitment rate to the BASIL+ trial. The secondary outcomes were the number of expressions of interest in the trial and the follow-up retention rate at 3 months post-randomisation. Results were compared for each group using a mixed-effect logistic regression model with trial site as a random effect. The cost-effectiveness of the SWAT intervention was also evaluated. Results Despite a small additional cost (£0.13) per participant, there was no evidence that participant recruitment, expressions of interest or retention was significantly affected by the inclusion of the one-page infographic. Conclusion Our results suggest that the inclusion of an infographic alongside the participant information sheet may not be the best way to improve recruitment and retention rates for RCTs. However, infographics continue to be effective tools for information delivery in healthcare settings, and further research is needed to explore their use in RCTs.

Photoelectrocatalytic Upgrading of Biomass Derivatives for Efficient C–N Coupling with Formamide

Exploring the coupling dynamics between accessibility of tourist attractions and tourism demand in Anhui Province

Tourist attractions, as core components of tourism product supply, play a crucial role in regional tourism development. Investigating the spatial relationship between the supply and demand of tourist attractions contributes to optimizing the spatial structure of regional tourism and promoting high-quality, balanced, and coordinated growth of the tourism industry. Taking high-grade tourist attractions in Anhui Province as the research object, this paper first analyzes the characteristics of accessibility using the time cost distance method and the standard deviational ellipse. Subsequently, it constructs a set of tourism demand indicators and employs the coupling coordination model and Markov chain method to evaluate the spatial coupling coordination between accessibility of tourist attractions and tourism demand. The results show a significant improvement in accessibility of tourist attractions from 2015 to 2024, with average travel time to tourist attractions at the county level decreasing from 65 to 41 minutes, and the proportion of areas reachable within 60 minutes rising from 62.5% to 92.3%. However, spatial disparities persist, particularly exhibiting persistent low accessibility in mountainous and peripheral areas. The coupling coordination levels between the accessibility of tourist attractions and tourism demand remained generally stable, with most counties classified into the moderate and high coordination categories. Spatial Markov analysis indicates that neighboring regions exert strong spatial spillover effects, influencing both the direction and magnitude of coordination level transitions. Notably, leap-level transitions were rare, while adjacent-level shifts dominated the dynamics. These findings underscore the importance of spatial context and infrastructure in shaping the interaction between tourism supply and demand. This study provides empirical evidence to support spatially differentiated planning and transportation investment strategies aimed at promoting balanced tourism development.

Heart’s desire

Enantioselective Construction of β-Substituted γ-Lactone through Catalytic Asymmetric Oshima–Utimoto Reaction: Divergent Total Syntheses of (−)-Podophyllotoxin and Its Eleven Congeners

Prevalence and determinants of depression, anxiety, and stress among secondary school students

Background By investigating the depression, anxiety and stress status of secondary school students, we further analysed the influencing factors of the changes in depression, anxiety and stress among secondary school students, so as to provide references for subsequent studies and interventions on adolescent mental health. Methods This study was a cross-sectional research study conducted in a city in Southwest China. A questionnaire survey was conducted during March-June 2022 among students attending secondary schools within a city. The surveyed secondary schools were not categorized as public or private. It mainly investigated the general information of middle school students, Depression-Anxiety-Stress Scale (DASS-21), and assessed the mental health status of middle school students. Results A total of 2,716 secondary school students were surveyed, 1,230 males (45.29%) and 1,486 females (54.71%). Among them, 24.4% of the secondary school students had depressive symptoms, 41.4% had anxiety symptoms, and 15.6% had stress; Through logistic regression analysis, attending high school, ranking <60% in academic performance, little or no family psychological support and peer psychological support were the main influencing factors. Conclusion The present study demonstrated that the high school student population, students with an academic ranking of <60%, and students who lacked family/peer psychological support were at higher risk for mental health. These findings provide an empirical basis for developing graded intervention strategies for specific risk factors..

‘Almost unimaginable’: these ants are different species but share a mother

Distribution of myogenic stem cell activator, hepatocyte growth factor, in skeletal muscle extracellular matrix and effect of short-term disuse and reloading

Hepatocyte growth factor (HGF) is a key myogenic stem cell (satellite cells) activator, that resides in the extracellular matrix (ECM). However, HGF distribution in the ECM varies depending on the muscle fiber type. Furthermore, aging impedes the binding of HGF to its receptors owing to nitration by peroxynitrite (ONOO - ). Though oxidative stress increases rapidly during muscle disuse atrophy, satellite cells are rapidly activated upon reloading. In this study, we investigated the distribution of HGF in the ECM in various muscle fiber types, and examined nitration of HGF in disuse and reloading models. Immunofluorescence staining was performed on the soleus (Sol), plantaris (Pla), and gastrocnemius (Gas) muscles of 10-week-old mice. Six mice were used to assess HGF distribution, while 12 mice, divided into control, disuse, and reloading groups were used for qualitative evaluation of nitrated HGF (nitroHGF). Student’s t-tests and the Bonferroni correction were employed for statistical analysis ( p  < 0.05/3 = 0.0167). In Sol muscle, type IIa and IIx muscle fibers exhibited higher HGF distribution in the ECM (61.5 ± 1.0% and 56.7 ± 1.1%, respectively) than type I fibers (32.3 ± 1.0%; p  < 0.001). In Pla and Gas muscle, type IIa 55.8 ± 0.9% and 58.8 ± 1.5%, respectively) and type IIx fibers (49.6 ± 0.9% and 48.9 ± 1.1%, respectively) had significantly higher HGF distribution in the ECM than type IIb fibers (18.6 ± 0.9% and 13.0 ± 1.0%; p  < 0.001, respectively). The amount of nitroHGF increased in the disuse group compared to that in the control group but decreased in the reloading group compared to that in the disuse group. This preferential HGF distribution around type IIa and IIx muscle fibers indicates a distinct mechanism for satellite cell activation, differing from the satellite cell-rich environment associated with type I fibers and the lower HGF association with type IIb fibers. Disuse-induced HGF nitration may inhibit satellite cell activation. Reloading likely triggers mechanisms that counteract nitration, enabling satellite cell reactivation in young muscle.

Separation-Free High-Purity Hydrogen Production via the Mechanochemical Ammonia–Silicon Reaction under Mild Conditions

GWOA: A multi-strategy enhanced whale optimization algorithm for engineering design optimization

This paper analyzes the shortcomings of the traditional Whale Optimization Algorithm (WOA), mainly including the tendency to fall into local optima, slow convergence speed, and insufficient global search ability for high-dimensional and complex optimization problems. An improved Whale Optimization Algorithm (GWOA) is proposed to overcome these issues. By integrating several improvement strategies, such as adaptive parameter adjustment, enhanced prey encircling, and sine-cosine search strategies, GWOA significantly enhances global search ability and convergence efficiency. However, GWOA increases computational complexity, which may lead to longer computation times when handling large-scale problems. It may also fall into local optima in high-dimensional cases. Several experiments were conducted to verify the effectiveness of GWOA. First, 23 classic benchmark functions were tested, covering unimodal, multimodal, and compositional optimization problems. GWOA was compared with other basic metaheuristic algorithms, excellent WOA variants, and the latest algorithms. Then, a comparative scalability experiment is performed on GWOA. The experimental results showed that GWOA achieved better convergence speed and solution accuracy than other algorithms in most test functions, especially in multimodal and compositional optimization problems, with an Overall Efficiency (OE) value of 74.46%. In engineering optimization problems, such as pressure vessel design and spring design, GWOA effectively reduced costs and met constraints, demonstrating stronger stability and optimization ability. In conclusion, GWOA significantly improves the global search ability, convergence speed, and solution stability through multi-strategy integration. It shows great potential in solving complex optimization problems and provides an efficient tool for engineering optimization applications.

Two ants, two species, one mother