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21 pages, 1435 KB  
Article
Growth Differentiation Factor 15 as a Biomarker of Cardiovascular Burden and Mortality in a Population-Based Cohort
by Beatriz Martín-Carro, Leticia Nieto-García, Clara Sánchez-Pablo, Alfonso Romero, Candelas Pérez del Villar, José Carlos Moyano-Maza, José María de Dios, David Cembrero-Fuciños, Estefanía Iglesias-Colino, Paz Muriel, Sara Cascón, Amalia Martín-Gallego, Baltasara Blázquez, Inmaculada Santolino, Lydia González-González, María Concepción Ledesma, Javier Maillo-Seco, Jesús Rodríguez-Nieto, Luis M. Rincón, María Isidoro-García and Pedro L Sánchezadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2026, 27(7), 3078; https://doi.org/10.3390/ijms27073078 (registering DOI) - 27 Mar 2026
Abstract
Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine strongly associated with aging, multimorbidity, and cardiovascular disease. Although prior studies have established its prognostic value in high-risk populations, its role in the general population remains less defined. The aim of this study was [...] Read more.
Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine strongly associated with aging, multimorbidity, and cardiovascular disease. Although prior studies have established its prognostic value in high-risk populations, its role in the general population remains less defined. The aim of this study was to determine if there is an association between plasma GDF15 levels, heart disease and mortality in a representative population-based cohort. We analyzed 1532 participants (mean age 55 years; 54.6% women) with available baseline plasma GDF15 concentrations. Participants were stratified according to an optimal cutoff of 1081 pg/mL, derived from ROC curve analysis for mortality. Associations with prevalent heart disease were assessed using multivariable logistic regression models adjusted for cardiovascular risk factors and NT-proBNP. Mortality was analyzed using Cox proportional hazards models, with model performance evaluated by C-index and time-dependent ROC curves. Individuals with GDF15 > 1081 pg/mL were older and exhibited a more adverse cardiometabolic profile with higher prevalence of comorbidities. Elevated GDF15 was independently associated with ischemic cardiomyopathy (OR 3.34, 95% CI: 1.38–8.11), particularly in men (OR 4.26, 95% CI: 1.40–12.96), but not in women. No independent associations were observed with arrhythmias, valvulopathy, or heart failure after adjustment for NT-proBNP. During a median follow-up of 6.2 years, 51 deaths occurred. Elevated GDF15 independently predicted all-cause mortality (HR 2.47, 95% CI: 1.19–5.13), though the effect was attenuated after adjustment for NT-proBNP. GDF15 improved model discrimination (ΔC-index = +0.01; LRT p = 0.011) and showed robust time-dependent predictive ability, with AUCs of 0.76, 0.82, and 0.85 at 2, 4, and 6 years, respectively. In this population-based cohort, elevated GDF15 identified individuals with an adverse health profile, was independently associated with ischemic cardiomyopathy in men, and predicted mortality. Although its incremental predictive value over NT-proBNP was modest, GDF15 could provide complementary biological information and may enhance multimarker strategies for cardiovascular risk stratification in the general population. Full article
16 pages, 2588 KB  
Article
Associations of Poincaré Plot-Derived Parameters with Heart Rate Variability and Autonomic Reflex Testing in a Real-World Clinical Population
by Branislav Milovanović, Nikola Marković, Maša Petrović, Aleksa Korugić and Milovan Bojić
Diagnostics 2026, 16(7), 1016; https://doi.org/10.3390/diagnostics16071016 (registering DOI) - 27 Mar 2026
Abstract
Background/Objectives: Poincaré plot analysis represents a nonlinear approach to heart rate variability (HRV) assessment, but the physiological meaning of several derived parameters remains unclear. This study aimed to evaluate associations between selected Poincaré plot-derived parameters, conventional HRV indices, and cardiovascular autonomic reflex tests [...] Read more.
Background/Objectives: Poincaré plot analysis represents a nonlinear approach to heart rate variability (HRV) assessment, but the physiological meaning of several derived parameters remains unclear. This study aimed to evaluate associations between selected Poincaré plot-derived parameters, conventional HRV indices, and cardiovascular autonomic reflex tests in a real-world clinical population. Methods: This observational study included 269 adult patients referred for evaluation of suspected autonomic dysfunction. All participants underwent short-term resting ECG, cardiovascular autonomic reflex testing, and 24 h Holter ECG monitoring. Poincaré plot-derived parameters were analyzed in relation to short- and long-term HRV measures using the Spearman correlation with false discovery rate correction, and group comparisons were performed based on reflex test results. Results: Several Poincaré plot-derived parameters showed strong correlations with long-term HRV indices. VLI and LA were primarily associated with global and long-term autonomic variability, whereas VAI and SA were more closely related to parasympathetic modulation. Associations with short-term HRV were generally weak. Lower values of selected parameters were observed in patients with abnormal parasympathetic reflex tests, while no significant differences were found in relation to orthostatic hypotension. Conclusions: Poincaré plot-derived parameters capture complementary aspects of autonomic regulation beyond conventional HRV indices and may enhance autonomic phenotyping in clinical settings. Full article
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17 pages, 1166 KB  
Article
An Integrated 60 GHz Radar and AI-Guided Infrared System for Non-Contact Heart Rate and Body Temperature Monitoring
by Sangwook Sim and Changgyun Kim
Appl. Sci. 2026, 16(7), 3272; https://doi.org/10.3390/app16073272 (registering DOI) - 27 Mar 2026
Abstract
The growing need for remote patient monitoring, accelerated by the global pandemic and an aging population, necessitates the development of advanced non-contact technologies for measuring vital signs. In this study, an integrated, non-contact system for accurately measuring heart rate (HR) and body temperature [...] Read more.
The growing need for remote patient monitoring, accelerated by the global pandemic and an aging population, necessitates the development of advanced non-contact technologies for measuring vital signs. In this study, an integrated, non-contact system for accurately measuring heart rate (HR) and body temperature (BT) is developed and validated. The proposed system combines a 60 GHz radar sensor and infrared (IR) sensor for HR and BT measurements, respectively, enhanced with advanced signal processing and an AI-based computer vision algorithm. A Window Filter and a Peak Uniformity algorithm were applied to the raw radar signal to mitigate noise and motion artifacts. For Temp measurement, an IR sensor with a narrow five-degree field of view (FOV) was integrated with a YOLO Pose-based tracking system using a camera and servo motors to automatically orient the sensor towards the user’s face. The system was validated with 30 healthy adult participants, benchmarked against a MAX30102 PPG sensor and Braun ThermoScan 7 for BT and BT measurements, respectively. The advanced signal processing reduced the HR Mean Absolute Error from 13.73 BPM to 5.28 BPM (p = 0.002), while the AI-guided IR sensor reduced the BT MAE from 4.10 °C to 1.64 °C (p < 0.001). These findings demonstrate that integrating 60 GHz radar with AI-driven tracking provides a promising approach for home-based trend monitoring. Full article
(This article belongs to the Special Issue AI-Based Biomedical Signal Processing—2nd Edition)
14 pages, 1334 KB  
Article
Transcriptome Sequencing and Identification of APOE Gene Polymorphisms, Their Expression and Their Relationship with Body Size Traits in Guizhou White Goats (Capra hircus)
by Wen-Ying Wang, Lin-Guang Dai, Jun-You Huang, Xing-Chao Song, Jin-Zhu Meng, Yuan-Yuan Zhao, Zhen-Yang Wu and Qing-Ming An
Animals 2026, 16(7), 1031; https://doi.org/10.3390/ani16071031 - 27 Mar 2026
Abstract
Carcass growth and development are crucial evaluation indicators influencing the economic efficiency of goats (Capra hircus). This study aimed to screen the nucleotide variation sites (SNPs) of the APOE gene in Guizhou white goats and explore the correlation between APOE gene [...] Read more.
Carcass growth and development are crucial evaluation indicators influencing the economic efficiency of goats (Capra hircus). This study aimed to screen the nucleotide variation sites (SNPs) of the APOE gene in Guizhou white goats and explore the correlation between APOE gene variations and body size traits, as APOE had been identified as a key candidate gene regulating growth and development in this breed through transcriptome sequencing screening. A total of 324 Guizhou white goats were used in this study for SNP detection, population genetic analysis, real-time fluorescence quantitative PCR (RT-qPCR) and association analysis. The results showed that one nucleotide mutation site (g.353 A > G) was detected in the APOE gene, which yielded two alleles (A and G) and three genotypes (AA, AG and GG). The site exhibited moderate polymorphism and conformed to Hardy–Weinberg equilibrium. The mRNA expression level of APOE in longissimus dorsi muscle was significantly higher in males than in females. Association analysis revealed a sex-specific effect of this locus on body size traits. The A allele and AA genotype were significantly associated with increased body weight and heart girth in females, whereas no significant effect was detected in males. Therefore, the identified APOE gene mutation site can serve as a candidate molecular marker for the early selection of growth traits in Guizhou white goats. Full article
(This article belongs to the Special Issue Genetics and Breeding for Enhancing Production Traits in Ruminants)
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18 pages, 3294 KB  
Systematic Review
Targeting the AMPK Pathway with Natural Products for Heart Failure: A Systematic Review of Preclinical Evidence
by Xiaoxiao Huang and Haitong Wan
Biomedicines 2026, 14(4), 765; https://doi.org/10.3390/biomedicines14040765 - 27 Mar 2026
Abstract
Background: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis, and its dysregulation is implicated in HF pathophysiology. Traditional Chinese Medicine (TCM) has been investigated in HF management, [...] Read more.
Background: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis, and its dysregulation is implicated in HF pathophysiology. Traditional Chinese Medicine (TCM) has been investigated in HF management, but a systematic synthesis of preclinical evidence on TCM-mediated AMPK modulation is lacking. Methods: PubMed and Web of Science were searched from January 2020 to December 2025 using a comprehensive strategy combining terms for AMPK, HF, and TCM. Studies were included if they were original research investigating TCM-derived compounds or formulas in HF models and reporting AMPK modulation. Study quality and evidence levels were assessed using predefined criteria. The review was conducted in accordance with PRISMA 2020 guidelines. Results: Of 243 records identified, 56 studies met the inclusion criteria (7 from database search and 49 from manual screening). Direct evidence for AMPK-dependent cardioprotection was limited. Cinnamaldehyde and paeoniflorin showed the most rigorous validation with confirmed target engagement and loss-of-function rescue. Berberine, crocin, ginsenoside Rb1, and honokiol demonstrated pathway-specific effects validated by pharmacological or genetic approaches. Most complex herbal formulas provided correlative evidence only, with Fuyu Decoction being a notable exception where AMPK agonist EX229 confirmed pathway involvement. Conclusions: Current evidence for TCM-mediated AMPK modulation in HF remains predominantly preliminary and correlative. Future research should prioritize causality validation using genetic models and human-relevant systems. Full article
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22 pages, 2321 KB  
Article
Drug-Resistant Gram-Positive Cocci as Etiological Factors of Cardiac Implantable Electronic Device Infections—Data from the EXTRACT Registry
by Danuta Łoboda, Sylwia Gładysz-Wańha, Michał Joniec, Eugeniusz Piłat, Robert D. Wojtyczka, Beata Sarecka-Hujar, Julia Staroń, Denis Swolana, Michał Gibiński, Karolina Simionescu, Sławomir Wilczyński and Krzysztof S. Gołba
Antibiotics 2026, 15(4), 345; https://doi.org/10.3390/antibiotics15040345 - 27 Mar 2026
Abstract
Introduction: Bacterial multidrug resistance (MDR) drives treatment with expensive, toxic, or pharmacokinetically suboptimal antibiotics. Objectives: To assess the prevalence of MDR Gram-positive cocci among isolates from cardiac implantable electronic device (CIED) infections at a Polish reference center. Methods: Data come from the “EXTRACT” [...] Read more.
Introduction: Bacterial multidrug resistance (MDR) drives treatment with expensive, toxic, or pharmacokinetically suboptimal antibiotics. Objectives: To assess the prevalence of MDR Gram-positive cocci among isolates from cardiac implantable electronic device (CIED) infections at a Polish reference center. Methods: Data come from the “EXTRACT” registry (ClinicalTrials.gov ID NCT05775783), which covers 702 transvenous lead extraction procedures. Blood samples and intraoperative swabs were collected from participants with CIED infection. Results: From 209 cases with isolated pocket infection (PI) (107, 51.2%) or systemic infections (102, 48.8%), 263 Gram-positive cocci were cultured. They were: coagulase-negative staphylococci (CoNS) (177, 67.3%), Staphylococcus aureus (62, 23.6%), enterococci (15, 5.7%), streptococci (8, 3.0%), and others (1, 0.4%). The highest MDR rate was among CoNS (46.9%). CoNS exhibited methicillin resistance (MR-CoNS) in 55.9% with co-resistance to macrolides (73.2%), lincosamides (51.0%), fluoroquinolones (56.1%), aminoglycosides (41.4%), tetracyclines (29.6%), and co-trimoxazole (29.3%). Resistance to daptomycin (5.3%) and linezolid (2.0%) in MR-CoNS was rare. The frequency of MDR S. aureus was 8.1%. Methicillin resistance in S. aureus (MRSA, 6.5%) co-occurred with resistance to macrolides/lincosamides and fluoroquinolones (100% for both) or linezolid (25.0%). All MDR staphylococci were vancomycin-susceptible. High-level aminoglycoside resistance (HLAR) in Enterococcus faecalis (53.8%) was accompanied by levofloxacin co-resistance (66.7%). Conversely, E. faecium HLAR (50.0%) strains showed 100.0% β-lactam resistance. Vancomycin-resistant enterococci (VRE) accounted for 6.7%; the VRE E. faecium strain was tigecycline- and linezolid-susceptible. Among viridans group streptococci, β-lactam and lincosamides resistance was common (40.0% for both), with 50.0% of co-resistance. Conclusions: Epidemiological data may improve the effectiveness of empirical antibiotic therapy for CIED-related infections. Full article
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16 pages, 652 KB  
Article
Effectiveness on Frailty of an eHealth-Based Rehabilitation Program in Older People with Acute Heart Failure and/or Acute Coronary Syndrome: Study Protocol for a Randomized Trial and Baseline Data of Participants
by Gaia Cattadori, Roberto F. E. Pedretti, Simona Sarzi Braga, Gabriele Maria Maglio, Monica Mancino, Tiziana Staine, Sara Mondaini, Luana Eramo, Valeria Pellegrini, Rosalba La Grotta, Denise Bruno, Eros Patuzzo, Giulia Matacchione, Angelica Giuliani, Rosa Carbonara, Angela Ferrulli, Maria Venneri, Chiara Osella, Lucrezia Quarto, Maddalena Genco, Irene D’Addabbo, Francesca Camicia, Lucia Palazzo, Attilio Caruso, Liana Spazzafumo, Fabiola Olivieri, Elena Tagliabue, Francesco Prattichizzo and Andrea Passantinoadd Show full author list remove Hide full author list
J. Clin. Med. 2026, 15(7), 2573; https://doi.org/10.3390/jcm15072573 - 27 Mar 2026
Abstract
Background: Frailty is highly prevalent among older adults with cardiovascular disease (CVD) and strongly predicts disability and mortality after cardiac events. Although cardiac rehabilitation (CR) improves prognosis, frail older patients often face barriers to participating in in-person programs. eHealth-based, home-delivered CR programs [...] Read more.
Background: Frailty is highly prevalent among older adults with cardiovascular disease (CVD) and strongly predicts disability and mortality after cardiac events. Although cardiac rehabilitation (CR) improves prognosis, frail older patients often face barriers to participating in in-person programs. eHealth-based, home-delivered CR programs incorporating tele-rehabilitation and remote monitoring may improve accessibility, yet evidence regarding their effectiveness on frailty status remains limited. Methods: We designed a multicenter, randomized, parallel-group trial enrolling people ≥65 years recently hospitalized for acute heart failure (AHF) and/or acute coronary syndrome (ACS). Participants were randomized 1:1 to an eHealth home-based tele-rehabilitation program or the usual care. The primary endpoint is frailty prevalence at follow-up, defined by an Essential Frailty Toolset (EFT) score ≥3, with co-primary outcomes being between-group differences in the mean levels of EFT and Short Physical Performance Battery (SPPB) scores after 3–6 months. Secondary endpoints include mortality and hospitalization, among others. Results: The full protocol and study procedures are reported. Between May 2024 and December 2025, 589 patients were screened at the two Italian centers involved; 442 met eligibility criteria and 209 were enrolled and randomized. Baseline characteristics were largely comparable between groups. The mean age was 77 ± 9 years, 70% were male, and 55% had ACS. Lower-than-expected enrollment was mainly attributable to refusal related to difficulties in using digital devices. Conclusions: This randomized trial will evaluate whether a multidomain, eHealth-based CR intervention can reduce the prevalence or degree of frailty in older people after AHF or ACS. We report the study protocol and baseline characteristics of the enrolled cohort, highlighting the challenge of digital illiteracy in contemporary older populations. Full article
(This article belongs to the Special Issue Clinical Management of Frailty)
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13 pages, 1345 KB  
Article
Acute Effects of Intermittent High-Intensity Exercise on Cardiac Autonomic Regulation in Male Non-Elite Badminton Players: A Multi-Point Time Series Analysis
by Heping Huang, Hongfei Jiang, Huiming Huang, Shenguang Li and Su Liu
Healthcare 2026, 14(7), 864; https://doi.org/10.3390/healthcare14070864 - 27 Mar 2026
Abstract
Objective: This study aimed to investigate the acute effects of intermittent high-intensity badminton court exercise on cardiac autonomic modulation in male non-elite badminton players. Methods: This study employed a single-arm, repeated-measures experimental design, recruiting 25 healthy male collegiate badminton players. Participants [...] Read more.
Objective: This study aimed to investigate the acute effects of intermittent high-intensity badminton court exercise on cardiac autonomic modulation in male non-elite badminton players. Methods: This study employed a single-arm, repeated-measures experimental design, recruiting 25 healthy male collegiate badminton players. Participants completed five sets of high-intensity intermittent court tests until exhaustion, followed by calculation of stress index (SI), time-domain (RMSSD and SDNN), and frequency-domain (LF, HF, and LF/HF ratio) parameters at rest using a certified heart rate variability (HRV) analyzer. Repeated-measures ANOVA and effect size (partial η2 and Hedges’ g) were used to assess changes and recovery trends of HRV parameters across time points: pre-test, immediate, 15 min, 24 h, and 48 h post-exercise. Results: (1) Stress index: The overall temporal trend showed statistical significance (p < 0.001, partial η2 = 0.236, large effect size). Compared to pre-test, immediate and 15 min post-exercise increases were 8.24 (95% CI: 0.63–15.85) and 9.84 (95% CI: 3.07–16.61) respectively, with Hedges’ g values of 0.77 and 0.99 (p < 0.001, large effect sizes). Values returned to pre-test levels at 24 and 48 h with no significant differences (p > 0.05). (2) Time-domain parameters: The overall temporal trend was statistically significant (p < 0.001, partial η2 = 0.553 for RMSSD and 0.586 for SDNN, both large effect sizes). Immediate post-exercise decreases in RMSSD and SDNN were 35.44 (95% CI: 21.95, 48.93) and 48.44 (95% CI: 32.49, 64.38) respectively, with Hedges’ g values of 2.31 and 2.78 (p < 0.001, large effect sizes). At 15 min, decreases were 31.64 (17.85, 45.42) and 41.48 (26.23, 56.72) respectively, with Hedges’ g values of 1.99 and 2.25 (p < 0.001, large effect sizes). Values returned to pre-test levels at 24 and 48 h with no significant differences (p > 0.05). (3) Frequency-domain parameters: Compared to pre-test, differences in LF, HF, and LF/HF were not statistically significant at any time point (all p > 0.05). Conclusions: Following high-intensity exercise leading to peripheral fatigue, cardiac autonomic function demonstrates a “suppression–recovery” dynamic pattern: cardiac stress levels increase significantly within 15 min post-exercise, with decreased overall HRV regulatory capacity and strong inhibition of parasympathetic activity; HRV status may return to baseline levels after 24 h. However, the frequency-domain indices of HRV showed no significant changes in response to the acute effects of high-intensity exercise. Full article
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28 pages, 5387 KB  
Article
Multi-Objective Optimized Differential Privacy with Interpretable Machine Learning for Brain Stroke and Heart Disease Diagnosis
by Mohammed Ibrahim Hussain, Arslan Munir, Safiul Haque Chowdhury, Mohammad Mamun and Muhammad Minoar Hossain
Algorithms 2026, 19(4), 260; https://doi.org/10.3390/a19040260 - 27 Mar 2026
Abstract
Brain stroke (BS) and heart disease (HD) are leading causes of global mortality and long-term disability, underscoring the critical need for early and accurate diagnostic tools. This research addresses the dual challenge of developing high-performance predictive models while ensuring the privacy of sensitive [...] Read more.
Brain stroke (BS) and heart disease (HD) are leading causes of global mortality and long-term disability, underscoring the critical need for early and accurate diagnostic tools. This research addresses the dual challenge of developing high-performance predictive models while ensuring the privacy of sensitive patient data. We propose a framework that integrates ensemble machine learning (ML) models with a formal differential privacy (DP) mechanism. Using a dataset of 5110 samples with clinical features, we evaluate Extreme Gradient Boosting (XGB), Random Forest (RF), Light Gradient Boosting Machine (LGBM), and Categorical Boosting (CAT) for BS and HD prediction. To protect individual privacy, we apply the Gaussian mechanism of DP with two probabilities of failure (POF) parameters (10–5 and 10–6) and a privacy budget ranging from 0.5 to 5.0. A key novelty of this work is the application of Pareto frontier multi-objective optimization (PFMOO) to systematically identify the optimal trade-off between model accuracy and privacy constraints. Our approach successfully identifies optimal, privacy-preserving models: XGB achieves top performance for BS prediction (92.3% accuracy, 92.29% F1 score), with a POF of 10–6, while RF excels for HD detection (95.61% accuracy, 97.8% precision), with a POF of 10–5. Furthermore, we employ explainable AI (XAI) techniques, SHAP and LIME, to provide interpretability of the model decisions, enhancing clinical trust. This research delivers a robust, interpretable, and privacy-conscious framework for early disease detection, offering a significant advancement over existing methods by holistically balancing accuracy, data security, and transparency. Full article
(This article belongs to the Special Issue 2026 and 2027 Selected Papers from Algorithms Editorial Board Members)
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9 pages, 712 KB  
Case Report
Successful Endoscope-Assisted Transcervical Insemination (TCI) in Dogs Using Sperm Recovered from Epididymides Stored at 5 °C for 24 h After Castration Prior to Semen Collection and Cryopreservation
by Mónika Bacsa, Eszter Szilágyi, Kristián Erdei, Linda Müller, Eszter Nagy, Balázs Attila Dobos, Tamás Radovits and Sándor Cseh
Vet. Sci. 2026, 13(4), 326; https://doi.org/10.3390/vetsci13040326 - 27 Mar 2026
Abstract
The recovery and cryopreservation of epididymal spermatozoa enable genetic preservation in male dogs that die unexpectedly or require castration; however, sperm collection is typically performed immediately after surgery, and artificial insemination is often surgical. This study aimed to evaluate whether epididymides stored at [...] Read more.
The recovery and cryopreservation of epididymal spermatozoa enable genetic preservation in male dogs that die unexpectedly or require castration; however, sperm collection is typically performed immediately after surgery, and artificial insemination is often surgical. This study aimed to evaluate whether epididymides stored at 4–5 °C for 24 h prior to sperm recovery retain fertilizing capacity after cryopreservation and whether pregnancy can be achieved using endoscopically guided transcervical intrauterine insemination. Testes and epididymides from an eight-month-old German Shepherd dog were stored in physiological saline at 4–5 °C for 24 h following castration. Spermatozoa were recovered from the cauda epididymis using single-incision aspiration, evaluated, frozen according to the Uppsala method, and stored in liquid nitrogen for two months. After thawing, 62 × 106 progressive motile spermatozoa were inseminated once into a bitch in heat using transcervical endoscopic guidance. Pregnancy was confirmed by ultrasonography, and nine healthy puppies were delivered at term. These findings demonstrate that 24 h refrigerated storage of the epididymis does not impair post-thaw fertilizing ability and that non-surgical transcervical intrauterine insemination represents an effective alternative to surgical techniques for the use of frozen–thawed epididymal semen in dogs. Full article
(This article belongs to the Section Veterinary Reproduction and Obstetrics)
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18 pages, 4940 KB  
Article
FGF23 Controls Myocardial Fibrosis Progression via Promoting Cardiac Fibroblast Proliferation and Activation in Mice
by Leyi Shen, Mingqi Hu, Mei Xue and Santie Li
Biology 2026, 15(7), 539; https://doi.org/10.3390/biology15070539 - 27 Mar 2026
Abstract
Heart failure (HF) is the leading cause of morbidity and mortality worldwide, while myocardial fibrosis acts as a pivotal hallmark, which exacerbates ventricular dysfunction and remodeling in HF. In this study, we found FGF23, a critical endocrine regulator, which regulates phosphate and vitamin [...] Read more.
Heart failure (HF) is the leading cause of morbidity and mortality worldwide, while myocardial fibrosis acts as a pivotal hallmark, which exacerbates ventricular dysfunction and remodeling in HF. In this study, we found FGF23, a critical endocrine regulator, which regulates phosphate and vitamin D metabolism, was significantly upregulated in fibrotic mouse hearts after transverse aortic constriction (TAC). By using the FGF23 monoclonal antibody, we found that inhibition of FGF23 alleviated TAC-induced cardiac fibrosis, while injection of recombinant FGF23 (rFGF23) protein exacerbated tissue fibrosis in mouse hearts after TAC. RNA sequencing indicated that FGF23 may promote cardiac fibroblast proliferation and activation in stressed mouse hearts. In human primary cardiac fibroblasts, rFGF23 treatment further upregulated the expression of Ki67, Cyclin D1, Cyclin E1, PCNA, α-SMA, and collagen 1A1 after TGF-β stimulation. Further results indicated that FGF23 promoted cardiac fibroblast proliferation and activation through FGFR4 and activated the downstream MAPK/ERK signaling. This study suggests a role of FGF23 in the regulation of myocardial fibrosis, which shows the potential of targeting FGF23 in the treatment of HF and cardiac fibrosis. Full article
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33 pages, 1768 KB  
Article
Continuous Emotion Recognition Using EDA-Graphs: A Graph Signal Processing Approach for Affective Dimension Estimation
by Luis R. Mercado-Diaz, Youngsun Kong, Josef Kundrát and Hugo F. Posada-Quintero
Appl. Sci. 2026, 16(7), 3240; https://doi.org/10.3390/app16073240 - 27 Mar 2026
Abstract
Emotion recognition from physiological signals has immense applications in healthcare and human–computer interaction. We developed an electrodermal activity (EDA)-graph signal processing pipeline that produces highly sensitive features for detecting the affective dimensions (arousal and valence) of emotions. Using the Continuously Annotated Signals of [...] Read more.
Emotion recognition from physiological signals has immense applications in healthcare and human–computer interaction. We developed an electrodermal activity (EDA)-graph signal processing pipeline that produces highly sensitive features for detecting the affective dimensions (arousal and valence) of emotions. Using the Continuously Annotated Signals of Emotion dataset, we compared our graph-based EDA features (EDA-graph) with traditional time- and frequency-domain EDA features and features derived from other signals (heart rate variability, pulse transit time, electromyography, skin temperature, and respiration) for detecting affective dimensions using machine learning regression models. The EDA-graph features showed superior performance in continuous affective dimension recognition compared to the most accurate state-of-the-art models, achieving RMSE values of 0.801 for arousal and 0.714 for valence. Furthermore, we used a variety of traditional and recently published datasets collected in laboratory and ambulatory settings to perform a comprehensive evaluation of the robust generalization capabilities of our approach across different emotional contexts. The models demonstrated exceptional performance in classifying emotional states across the datasets, achieving 98.2% accuracy in detecting positive, negative, and mixed emotions; 92.75% in discriminating between emotions (relaxed, amused, bored, scared, and neutral); and 86.54% in detecting stress vs. no stress. These results highlight the potential of a graph-based analysis of EDA in emotion recognition systems in different contexts, especially for real-world applications. Full article
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14 pages, 594 KB  
Article
Influence of Phenotypes on Short-Term Outcomes in Hospitalized Heart Failure with Preserved Ejection Fraction—Insights from a North-Eastern Romanian Cohort
by Victoria Mutruc, Mara Sânziana Sângeap, Cristina Bologa, Victorița Sorodoc, Ovidiu Rusalim Petriș, Oana Sîrbu, Bianca Codrina Morărașu, Luiza Elena Corneanu, Elisabeta Jaba, Laurențiu Șorodoc and Cătălina Lionte
Med. Sci. 2026, 14(2), 167; https://doi.org/10.3390/medsci14020167 - 27 Mar 2026
Abstract
Background/Objectives: There are significant gaps in knowledge regarding the heterogeneity of heart failure (HF) phenotypes, particularly among patients with preserved left ventricular ejection fraction (HFpEF). Our aim was to identify phenotypes within the hospitalized North-Eastern Romanian HFpEF cohort and their impact on [...] Read more.
Background/Objectives: There are significant gaps in knowledge regarding the heterogeneity of heart failure (HF) phenotypes, particularly among patients with preserved left ventricular ejection fraction (HFpEF). Our aim was to identify phenotypes within the hospitalized North-Eastern Romanian HFpEF cohort and their impact on short-term outcomes. Methods and Results: We derived a cluster model from 924 patients with HFpEF hospitalized over an 18-month interval in the Internal Medicine II Department of the “Sf. Spiridon” Emergency Clinical County Hospital in Iași, Romania. The median age of the patients was 74 years [range 30–101], 59.8% were women, and the most frequent comorbidities were arterial hypertension (93.2%), valvular heart disease (68.7%), atherosclerotic cardiovascular disease (ASCVD, 64.6%) and atrial fibrillation (43%). Statistical analysis identified five distinct phenotypes: cluster 1 (21.6% of patients) consisted of normal-weight patients with valvular disease predominance; cluster 2 (18.2%) described a severe cardiometabolic phenotype; cluster 3 (19.6%) defined a young, hypertensive, and atherosclerotic phenotype; cluster 4 (21.26%) described a hypertensive–atrial fibrillation phenotype; and cluster 5 (18.9%) included elderly, hypertensive non-diabetic patients with severe vascular burden (ASCVD 100%). Conclusions: This study defines five distinct phenotypes within the HFpEF population in our region which differ in terms of clinical characteristics and heart failure pharmacological therapy. These results confirm the significant heterogeneity of HFpEF. The identified phenotypes were not associated with significant differences in composite short-term outcomes, including in-hospital mortality and 30-day rehospitalization for heart failure. Full article
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14 pages, 1070 KB  
Article
Hemoglobin-to-Red Cell Distribution Width Ratio as a Prognostic Marker in Decompensated Heart Failure Patients: A Prospective Observational Study
by Ruxandra Maria Christodorescu, Călin Muntean, Minodora Andor, Daniel Lighezan, Adina Pop Moldovan, Andrei Blajevschi, Samuel Ardelean and Dan Darabanțiu
Life 2026, 16(4), 551; https://doi.org/10.3390/life16040551 - 27 Mar 2026
Abstract
Background and Methods: This prospective observational study investigated the prognostic value of the hemoglobin-to-red cell distribution width ratio (HRR) in 278 patients hospitalized with decompensated heart failure (HF). The primary endpoint was a composite of all-cause mortality or HF rehospitalization at 12 months. [...] Read more.
Background and Methods: This prospective observational study investigated the prognostic value of the hemoglobin-to-red cell distribution width ratio (HRR) in 278 patients hospitalized with decompensated heart failure (HF). The primary endpoint was a composite of all-cause mortality or HF rehospitalization at 12 months. Multivariable Cox regression was employed to adjust for risk factors including age, sex, NT-proBNP, LVEF, and eGFR. Results: The median HRR was 0.89. During follow-up, the primary endpoint occurred in 167 (60.1%) patients. Unadjusted analysis showed a lower HRR was significantly associated with reduced event-free survival (log-rank p = 0.027). However, after multivariable adjustment, this association was no longer statistically significant (p = 0.240). Older age and male sex remained independent predictors. Conclusions: In patients with decompensated HF, a lower baseline HRR correlates with increased risk but does not maintain independent prognostic value after adjusting for powerful confounders. HRR may serve as a simple, initial marker of risk rather than an independent predictor. Full article
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20 pages, 264 KB  
Article
Collaboration Between Nurses and Patients’ Families in Managing Chronic Heart Failure in Older Adults: A Qualitative Study
by Abdulaziz M. Alodhailah, Albandari Almutairi, Thurayya Eid, Rayhanah R. Almutairi, Asrar S. Almutairi, Ashwaq A. Almutairi, Waleed M. Alshehri, Bader M. Almutairy and Faihan F. Alshaibany
Healthcare 2026, 14(7), 853; https://doi.org/10.3390/healthcare14070853 - 27 Mar 2026
Abstract
Background: Chronic heart failure (CHF) in older adults requires sustained self-management and close follow-up, yet day-to-day care is often carried out by families with support from primary healthcare nurses. In Saudi Arabia, where family caregiving is culturally normative, collaboration between nurses and [...] Read more.
Background: Chronic heart failure (CHF) in older adults requires sustained self-management and close follow-up, yet day-to-day care is often carried out by families with support from primary healthcare nurses. In Saudi Arabia, where family caregiving is culturally normative, collaboration between nurses and patients’ families may be pivotal to effective CHF management, but remains insufficiently understood in primary healthcare contexts. Methods: A qualitative study informed by an interpretive phenomenological approach was conducted. Participants (n = 24; 12 nurses and 12 family caregivers) were recruited using purposive sampling from primary healthcare centers in Riyadh, Saudi Arabia. In-depth, semi-structured interviews were conducted in Arabic or English, audio-recorded, transcribed verbatim, and analyzed using reflexive thematic analysis following Braun and Clarke’s six-phase framework. Strategies to enhance trustworthiness included member checking, peer debriefing, maintenance of an audit trail, and reflexive journaling. Results: Twenty-four participants (12 nurses and 12 family caregivers) were interviewed. Four interrelated themes were generated from both nurses’ and family caregivers’ accounts. (1) “We Are Caring Together”: Collaboration was experienced as shared responsibility for daily CHF management, grounded in trust; (2) Navigating Roles and Boundaries: Participants described unclear expectations, role overlap, and tension between professional authority and family knowledge; (3) Communication as the Engine of Collaboration: Effective partnerships depended on clear information exchange, caregiver-tailored education, and continuity of contact, while communication gaps created uncertainty and delayed support-seeking; and (4) Cultural and System Constraints Shaping Collaboration: Strong family obligation motivated caregiving but also intensified moral pressure and limited help-seeking, while time pressure and fragmented services constrained meaningful engagement and continuity across settings. Conclusions: Nurse–family collaboration in CHF management is relational, shaped by trust, role negotiation, and communication, and constrained by cultural norms and system pressures. This study contributes to the literature by demonstrating how moral obligation, hierarchical professional norms, and system fragmentation distinctively shape collaboration in the Saudi primary care context, extending existing conceptualizations derived primarily from Western individualist settings. Strengthening collaboration requires explicit role clarification, health literacy–informed caregiver education, continuity of contact, and organizational supports. Findings are limited by purposive sampling, single-city context, and exclusion of patient perspectives. Full article
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