Browse Articles

B-cell signatures characterize the immune landscape and predict LUAD prognosis via the integration of scRNA-seq and bulk RNA-seq

Hydrothermal treatment of yeast cell wall generates potent anti-proliferative agents targeting MCF7 breast cancer cells effectively even under culture conditions separated by a plastic wall

Traditionally, the yeast cell wall (YCW) has limited applications because of its low solubility. To overcome this, a novel method was developed using a hydrothermal reaction to enhance its solubility and decrease its viscosity; this resulted in the production of a soluble form of YCW, known as the YCW treated with hydrothermal reaction (YCW-H), with broader chemical composition. However, the biological impact of YCW-H is unclear, excluding its reported plant growth-promotion by effectively regulating soil microspheres. This study investigated the potential of YCW-H to inhibit MCF-7 breast cancer cell proliferation. YCW-H demonstrated significant anti-proliferative effects on MCF7 cells, reducing cell growth by 58.7% ± 6.9 even when physically separated from the cells by a plastic wall. The observation suggests the presence of a diffusible factor against cell proliferation in YCW-H, a phenomenon not observed in the presence of untreated YCW. Reactive carbon species (RCS) generated during the hydrothermal treatment of YCW could be responsible for the effect. The addition of Fe(III) ions into YCW-H further amplified RCS production and elevated its inhibitory activity by about 10% across the plastic barrier. Radical adduct concentration of H2O in a tube which was incubated in YCW-H was 0.47 μmol/L, indicating that radicals migrated into the water through the plastic wall. The concentration of radical adducts in H2O in a tube exposed to YCW-H with Fe(III) ions further increased to 0.51 μmol/L, indicating that the growth inhibition was correlated with the increased RCS levels. Furthermore, flow cytometry analysis revealed the cytotoxic effects of YCW-H, indicating YCW-H is applicable to cancer therapy. Therefore, the findings highlight the pivotal role of RCS in the YCW-H anti-cancer activity, suggesting its potential as a promising candidate for the development of novel medical devices for cancer treatment.

Early detection of Parkinson’s disease using a multi area graph convolutional network

Optimal dose and duration of iron supplementation for treating iron deficiency anaemia in children and adolescents: A systematic review and meta-analysis

Introduction Iron deficiency anaemia (IDA) accounts for nearly two-thirds of all anaemia cases globally. Despite the widespread use of iron supplementation, the optimal dose and duration for treating IDA remain unclear. In this study, we aimed to determine the most effective dose and duration of iron supplementation for improving haemoglobin (Hb) levels in children and adolescents (≤19 years) with IDA. Methods A systematic review and meta-analysis were conducted. We searched MEDLINE, Embase, CINAHL, and the Cochrane Library for peer-reviewed studies published between 2013 and 2024. The interventions included iron supplementation with a defined dose and duration of at least 30 days. Comparators were placebo, no treatment, or alternative regimens. The outcome was the change in Hb levels. Eligible studies included IDA cases diagnosed through ferritin level measurements in healthy individuals. Studies involving pregnant women or children with underlying conditions were excluded. A meta-analysis was performed using standardized mean differences to pool effect sizes for Hb improvement with 95% confidence intervals (CIs). Subgroup analyses were performed for different treatment durations (<3 months, 3–6 months, >6 months) and dosage categories (<5 mg/kg/day, 5–10 mg/kg/day, >10 mg/kg/day). A random-effects meta-regression model was used to determine the optimal dose and duration, accounting for known covariates affecting Hb improvement. Results A total of 28 studies with 8,829 participants from 16 countries were included. The pooled effect size for Hb improvement was 2.01 gm/dL (95% CI: 1.48–2.54, p < 0.001). Iron supplementation for less than 3 months showed the highest significant effect size (2.39 gm/dL, 95% CI: 0.72–4.07), followed by treatments exceeding 6 months (1.93 gm/dL, 95% CI: 0.09–3.77). The lowest effect size was observed in treatments lasting 3–6 months (1.58 gm/dL, 95% CI: 0.93–2.23). Low-dose iron supplementation (<5 mg/kg/day) demonstrated favourable trends in Hb improvement, particularly in individuals with lower baseline Hb levels. Oral ferrous sulphate had a significant effect (2.03 gm/dL, 95% CI: 1.24–2.82), while parenteral ferric Carboxymaltose showed consistent efficacy. Conclusion Low-dose iron supplementation (<5 mg/kg/day) combined with treatment durations of either less than 3 months or more than 6 months, is optimal for improving Hb levels in children and adolescents with IDA. Tailoring treatment based on baseline Hb levels and anaemia severity is essential. These findings provide evidence to support updated guidelines on iron supplementation in paediatric and adolescent populations and inform national anaemia management programmes. Trial registration Prospero registration number: This study was registered with PROSPERO (CRD42024541773).

Transformer-based heart language model with electrocardiogram annotations

Acute fatigue in indoor court-based team sports: A systematic review

Fatigue in team sports has been widely researched, with a number of systematic reviews summarising the acute (i.e., within 48-hours) response in outdoor sports. However, the fatigue response to indoor court-based sports is likely to differ to outdoor sports due to smaller playing fields, harder surfaces, and greater match frequencies, thus should be considered separately to outdoor sports. Therefore, this study aimed to conduct a systematic review on acute fatigue in indoor court-based team-sport, identify methods and markers used to measure acute fatigue, and describe acute fatigue responses. A systematic search of the electronic databases (PubMed, SPORTDiscus, MEDLINE and CINHAL) was conducted from earliest record to June 2023. Included studies investigated either a physical, technical, perceptual, or physiological response taken before and after training, match, or tournament play. One-hundred and eight studies were included, measuring 142 markers of fatigue. Large variability in methods, fatigue markers and timeline of measurements were present. Cortisol (n =  43), creatine kinase (n =  28), countermovement jump (n =  26) and testosterone (n =  23) were the most frequently examined fatigue markers. Creatine kinase displayed the most consistent trend, increasing 10–204% at 24-hours across sports. There is large variability across studies in the methods and markers used to determine acute fatigue responses in indoor court-based team sports. Future researchers should focus on markers that display high reliability and transfer to practice. The robustness of studies may be increased by ensuring appropriate methods and timescale of fatigue marker measurement are used. Further research is required to determine which combination of markers best describes a fatigue response.

Cell-specific genetic expression profile of antennal glia in Drosophila reveals candidate genes in neuron-glia interactions

Validation of ICD-10 codes used to identify the main reason for hospitalization due to hyponatremia in Sweden

Purpose Hyponatremia is the most common electrolyte disorder, with potentially serious consequences. Studies validating hyponatremia used as a principal diagnosis are lacking. Studying principal diagnoses is important since it indicates the main reason for inpatient care. The aim of this study was to assess the validity of principal diagnoses of hyponatremia according to the International Classification of Diseases, tenth revision (ICD-10) in patients discharged from hospital. Methods Three independent reviewers retrospectively analyzed medical records of 428 hospitalized patients, ≥18 years old, discharged with a principal diagnosis of either hyponatremia or syndrome of inappropriate anti-diuretic hormone secretion (SIADH) from three different hospitals during 2014–2017. The positive predictive value of hyponatremia as a principal diagnosis was calculated. Results The median age of the studied population was 73 (IQR 64–81) years and 69% were women. The range of sodium levels was < 100 to 139 mmol/L. The mean sodium level was 119 mmol/L. Of the patients 27% were treated in an intensive care unit (ICU)/high dependency unit (HDU). Hyponatremia was deemed to be the principal cause of inpatient care in 411 out of 428 patients, corresponding to a positive predictive value for hyponatremia as a principal diagnosis of 96% (CI 95% 94–98). Conclusions The current study showed that 19 diagnoses out of 20 were correct implying a high validity. Thus, a principal diagnosis of hyponatremia, appears to be a useful measure in clinical and epidemiological studies aiming to target a clinically relevant consequence of hyponatremia in hospitalized patients.

High intensity interval training alters gene expression linked to mitochondrial biogenesis and dynamics in high fat diet fed rats

Abstract A High-Fat Diet (HFD) leads to disruption of mitochondrial biogenesis and dynamics. Exercise training, especially High-Intensity Interval Training (HIIT) increases mitochondrial biogenesis and dynamics. The present study aimed to investigate the effect of a period of HIIT with and without HFD consumption on the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1-α), Mitofusins-2 (Mfn2), Optic atrophy-1 (Opa1), Dynamin-related protein-1 (Drp1) and mitochondrial Fission protein-1 (Fis1) genes as indicators of mitochondrial biogenesis and dynamics function in the soleus muscle of male Wistar rats. Twenty-four healthy male Wistar rats were randomly divided into four groups: (1) Control, (2) Control + HIIT, (3) HFD, and (4) HFD + HIIT. The HIIT training protocol lasted for 10 weeks with a frequency of 3 sessions per week. The Real-Time Quantitative Reverse Transcription PCR method was used to investigate the gene expression. One-way ANOVA and Fisher’s post-hoc analyses were used to examine group differences. HFD consumption caused an increase in weight (P < 0.05), the expression of Drp1 and Fis1 genes (P < 0.001), and a decreased expression of Pgc1-α, Mfn2, and Opa1 genes (P < 0.001). HIIT training increased the expression of PGC1-α (P = 0.009), Mfn2 (P < 0.004), and Opa1 (P < 0.011) genes, while it decreased the expression of Drp1 (P = 0.003) and Fis1 genes (P = 0.027). These findings suggest that HIIT can counteract the negative effects of HFD on mitochondrial function by modulating gene expression related to mitochondrial biogenesis and dynamics.

4D trajectory prediction and conflict detection in terminal areas based on an improved convolutional network

At present, the passenger traffic volume of civil aviation is gradually increasing, and the scale of the airline network is gradually expanding. In order to optimize the air traffic service mode more safely and scientifically, the International Civil Aviation Organization (ICAO) has proposed a new concept of trajectory based operation (TBO). According to the basic principle and core structure of TBO, aiming at improving the accuracy of Four Dimensional (4D) Trajectory prediction and the reliability of multi-trajectory flight conflict detection, the trajectory prediction model is established by using convolutional neural networks-bidirectional gated recurrent unit (CNN-BiGRU), and the conflict evaluation of prediction results is realized by using trajectory distance detection function. The simulation experiment shows that the simulation experiment is carried out by introducing the real automatic dependent surveillance-broadcast (ADS-B) historical track data in the terminal area of the busy airport. The experimental results are compared with the experimental results of the single long short-term memory (LSTM) model and the gated recurrent unit (GRU) model in the same data set. The results show that the CNN-BiGRU trajectory prediction model is superior to the comparison model in many evaluation indexes, and the conflict detection results can be evaluated for the future 800 seconds interval of the two trajectories.

Developing a nomogram model for predicting non-obstructive azoospermia using machine learning techniques

Integrated metagenomic and metabolomic analyses of the effects of total flavonoids of Rhizoma Drynariae on reducing ovariectomized-induced osteoporosis by regulating gut microbiota and related metabolites

TFRD has been widely used in China to treat osteoporosis (OP). However, the specific molecular mechanism of TFRD against OP has not been fully clarified. Our previous studies have also proved that TFRD could attenuate OP and the clinical equivalent dose of 67.5mg/kg/d is the effective dose for TFRD treating OP. Therefore, this study used 67.5mg/kg as the dosage of TFRD in combination with multi omics to investigate the mechanism of action of TFRD in the treatment of OP. The aim of this study was to further elucidate molecular mechanism of TFRD for treating OP based on metagenomic and metabolomic analyses. In this study, hematoxylin-eosin (H&E) staining, micro computed tomography (micro-CT) and bone mineral density (BMD) analysis were used to observe pharmacological effects of TFRD against ovariectomized (OVX)-induced OP. Subsequently, multiomics analysis including metagenomics, untargeted and short chain fatty acids (SCFAs) metabolomics were carried out to identify whether the anti-osteoporosis mechanism of TFRD correlated with gut microbiota and related metabolites. Our results indicate that TFRD could improve the microstructure and density of trabecular bone in OVX rats. 17 differential species, which mainly from Akkermansia, Bacteroides, and Phascolarctobacterium genus, 14 related differential metabolites and acetic acid in SCFAs were significantly altered by OVX and reversed by TFRD. Furthermore, according to results of untargeted metabolomics analysis, it was found that several metabolic pathways such as phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis and so on might play an important role in TFRD against OP. In order to further study the relationship between gut microbiota and related metabolites, spearman correlation analysis was used, and showed that gut microbiota such as Akkermansia muciniphila might be closely related to several metabolites and metabolic pathways. These findings suggest that TFRD treatment could reduce the effects of OVX-induced OP by altering community composition and abundance of gut microbiota, regulating metabolites and SCFAs. It was speculated that the gut microbiota especially Akkermansia muciniphila and related metabolites might play an important role in TFRD against OP, and deserve further study by follow-up experiment. This conclusion provides new theoretical support for mechanism research of TFRD against OP.

Genome-wide identification and functional validation of the WW domain containing oxidoreductase gene associated with sleep duration

Specialised palliative care in nursing homes – Retrospective analysis on the basis of claims data

Background The aim of palliative care is to improve the quality of life of patients with a life limiting illness. In Germany, nursing homes are increasingly the last residence and a common place of death for older people. This renders these institutions as places with a high need for palliative care. However, the frequency of specialised palliative care services in nursing homes in Germany is often low. Objectives The aim of this study is 1) to analyse the types and frequencies of services provided by specialised ambulatory palliative care teams in nursing homes in the German federal state of Mecklenburg-Western Pomerania, and 2) to examine whether the frequency of specialised palliative services in nursing homes is comparable to patients living in their private homes. Methods The analysis was based on data of the association of statutory health insurance physicians Mecklenburg-Western Pomerania (Germany), data of the statutory health insurance BARMER, and population data. All patients who received specialised ambulatory palliative care in nursing homes in the years 2015–2017 were included in the analysis. For the comparison of the utilisation of specialised ambulatory palliative care in nursing homes with patients in private households, two comparable groups were created using claims, population data and life-year-mortality tables of the general population. It was assumed that people ≥80 years with a life expectancy of <12 months were potential candidates for the utilisation of palliative care. Data were analysed using descriptive statistics and Chi-Square tests. Results In Mecklenburg-Western Pomerania, 6,096 patients received specialised ambulatory palliative care in the time period 2015 to 2017. Of these, 16.0% (n = 978) were nursing home residents. The median duration of specialised ambulatory palliative care in nursing homes was 12.0 days, for people in private households 27.2 days. The rate of patients receiving specialised ambulatory palliative care in nursing homes was 4.7%, for people in the comparable group in private households it was 9.2% (p < 0.0001). Conclusion Only a small number of nursing home residents received specialised ambulatory palliative care in their last year of life. The rate among those living in their own homes is about twice as high. The results indicate that nursing home residents may have less access to specialised ambulatory palliative care than patients living in private households. Specialised ambulatory palliative care services provision in nursing homes should be improved.

Physicochemical properties of plasma-activated water and associated antimicrobial activity against fungi and bacteria

Evaluation of four regimens of methyl aminolevulinate mediated by red light to treat actinic keratoses: A randomized controlled clinical protocol

The multifocality of actinic keratosis (AK), the unpredictability of lesion evolution with potential progression to squamous cell carcinoma (SCC), and the consequent risk of local extension and metastasis, alongside the recent development of new therapies, make the selection of a therapeutic regimen challenging. The increasing incidence of this condition is associated with economic costs and its impact on quality of life, which has fostered interest in studying protocols for treating this skin condition. The topical application of 16% methyl aminolevulinate (MAL) is well-established in the literature for its local therapeutic effects and ease of application. However, the high cost of medication, long incubation time, and adverse effects such as itching and burning in some patients limit the dissemination of this treatment. Studies are needed to test other protocols of this promising therapy to increase acceptance among patients and professionals. Therefore, the objective of this protocol is to compare the efficacy of the topical application of MAL at concentrations of 8% and 16%, mediated by red light, as well as to evaluate the impact of different incubation times (1 or 3 hours) in the treatment of actinic keratoses on the face, with a 6-month follow-up. This parallel-arm, 6-month follow-up randomized controlled, double-blind clinical protocol will consist of 4 groups: G1 - Control Group - MAL 16% irradiated with 643 nm and 75 J/cm2 and 3-hour incubation time (n = 36), G2 - MAL 16% and 1-hour incubation (n = 36), G3 - MAL 8% - 3 hours (n = 36), and G4 - MAL 8% - 1 hour (n = 36). The primary outcome will be the complete remission of the lesion at six months. Secondary outcomes will include treatment success (75% reduction in the initial number of lesions), recurrence rate, emergence of SCC, incidence of adverse effects, and improvement in skin texture, wrinkles, and pigmentation using a validated scale. All outcomes will be assessed at 30 days, 3, and 6 months. At six months, quality of life will be assessed using the Actinic Keratosis Quality of Life questionnaire (AKQoL) and Face-Q. If data are normal, they will be subjected to 3-way ANOVA and presented as means ± standard deviation (SD). Otherwise, they will be presented as median and interquartile range and compared using the Kruskall-Wallis and Friedman tests. Categorical variables will be evaluated with the chi-square, Fisher’s exact, or likelihood ratio tests. A p-value < 0.05 will be considered significant.

Comparative analysis of Legionella lytica genome identifies specific metabolic traits and virulence factors

Abstract The complete genome of Legionella lytica PCM 2298 was sequenced and analyzed to provide insights into its genomic structure, virulence potential, and evolutionary position within the Legionella genus. The genome comprised a 3.2 Mbp chromosome and two plasmids, pLlyPCM2298_1 and pLlyPCM2298_2, contributing to a total genome size of 3.7 Mbp. Functional annotation identified 3,165 coding sequences, including genes associated with known virulence factors such as the major outer membrane protein (MOMP), the macrophage infectivity potentiator (Mip), and a comprehensive set of secretion systems (type II, type IVA, and type IVB Dot/Icm type IV secretion system). Notably, L. lytica contributed 383 unique genes to the Legionella pangenome, with 232 identified effector proteins, of which 35 were plasmid-encoded. The identification of unique genes, particularly those on plasmids, suggests an evolutionary strategy favoring horizontal gene transfer and niche adaptation. The effector repertoire included proteins with domains characteristic of host interaction strategies, such as ankyrin repeats and protein kinases. Comparative analyses showed that while L. lytica shares core virulence traits with other Legionella species, it has distinct features that may contribute to its adaptability and pathogenic potential. These findings underscore the genomic diversity within the genus and contribute to a deeper understanding of Legionella’s ecological and clinical significance. A custom web application was developed using the R Shiny library, enabling users to interactively explore the expanded Legionella pangenome through UpSet plots.

Process evaluation of Tuberculosis infection control and prevention practice at public health facilities in Tegede district, Northwest Ethiopia: Facility-based cross-sectional design

Background Tuberculosis Infection Prevention and Control practice (TB-IPC) is crucial to prevent nosocomial transmission of Tuberculosis (TB), especially in high-burden settings like Ethiopia. However, studies show that TB infection control practices among healthcare workers in Ethiopia are suboptimal. The study aims to evaluate TB-IPC practices at public health facilities in Tegede district, Northwest Ethiopia. Methods A facility-based cross-sectional design with mixed methods and a formative approach was used to evaluate the TB-IPC from May 1 to June 30, 2023. The practice was assessed using availability, compliance, and acceptability dimensions with 31 indicators. The quantitative data was collected from 525 clients using structured questionnaires. The data were coded, entered into EpiData version 4.6, and exported to SPSS version 25 for analysis. Binary and multivariable logistic regression analyses were used to identify the predictor variables associated with client satisfaction. Furthermore, non-participatory direct observations, document reviews, and resource inventories were conducted. In the qualitative study, key informants were interviewed, and qualitative data were transcribed, translated, coded, and analyzed manually in themes. Result The overall implementation of TB-IPC practice was 54.4%. The availability dimension was 50.4%, compliance was 67.2%, and acceptability was 43.4%. A total of 525 clients participated, with a response rate of 96.2%. In the multivariable logistic regression analysis, occupation was the predicator variable with a p-value of <0.05. In total, 134 (25.5%) clients, with a 95% CI [22.0%, 29.4%], were satisfied with TB-IPC practices at public health centers in Tegede district. Conclusion The overall implementation of TB-IPC practices at public health facilities in Tegede district is currently poor and requires urgent improvement. Based on stakeholders’ judgment criteria, the dimensions of availability, compliance, and acceptability were rated as poor, fair, and poor, respectively. These findings provide a baseline understanding of how TB-IPC practices are implemented in Tegede district.

Author Correction: On modified Mittag–Leffler coupled hybrid fractional system constrained by Dhage hybrid fixed point in Banach algebra

A novel trajectory learning method for robotic arms based on Gaussian Mixture Model and k-value selection algorithm

In the field of robotic arm trajectory imitation learning, Gaussian Mixture Models are widely used for their ability to capture the characteristics of complex trajectories. However, one major challenge in utilizing these models lies in the initialization process, particularly in determining the number of Gaussian kernels, or the k-value. The choice of the k-value significantly impacts the model’s performance, and traditional methods, such as random selection or selection based on empirical knowledge, often lead to suboptimal outcomes. To address this challenge, this paper proposes a novel trajectory learning method for robotic arms that combines Gaussian Mixture Model with a k-value selection algorithm. The proposed approach leverages the principles of the elbow method along with the properties of exponential functions, correction terms, and weight adjustments to accurately determine the optimal k-value. Next, k-means clustering is applied with the optimal k-value to initialize the parameters of the Gaussian Mixture Model, which are then refined and trained through the Expectation-Maximization algorithm. The resulting model parameters are then employed in Gaussian Mixture Regression to generate the robotic arm trajectories. The effectiveness of the proposed method is validated through both simulation experiments with two-dimensional theoretical nonlinear dynamic systems and physical experiments with actual robotic arm data. Experimental results demonstrate that, compared to the traditional Gaussian Mixture Model approach, the proposed method improves trajectory accuracy by more than 15%, as shown by reductions in both the Mean Absolute Error and the Root Mean Square Error. These results highlight that the proposed method significantly enhances the accuracy and efficiency of robotic arm trajectory generation, providing a promising solution for improving robotic manipulation tasks.