Life, Volume 15, Issue 7 (July 2025) – 170 articles

(1) Background: Occupational exposure to asbestos remains a significant public health concern due to its association with pleural cancer and other cancers. This cohort study examines the incidence of asbestos-related diseases among railway carriage maintenance workers exposed to asbestos between 1960 and 1979 in Bologna, Italy. (2) Methods: A cohort of 2197 male workers was followed from 1960 onwards, with data collected on asbestos exposure, smoking habits, and mortality outcomes. The association of asbestos exposure and smoking with the risk of pleural cancer and lung cancer was assessed using Cox proportional hazards regression models. (3) Results: This study identified a substantial burden of asbestos-related pleural cancer, with an exponential increase in risk over time since the beginning of exposure. Our results suggest the lack of a multiplicative effect of asbestos exposure and smoking on lung cancer risk. The Cox models showed a significant association between smoking and lung cancer risk, with a hazard ratio of 3.26 (95% CI: 1.10–9.64, p = 0.03), less significant for asbestos exposure, with a hazard ratio of 1.42 (95% CI: 0.66–3.06). (4) Conclusions: This study provides valuable insights into the long-term health effects of occupational asbestos exposure and underscores the complex interaction between asbestos exposure and smoking in the development of lung cancer. Full article

Aphelenchoides besseyi is considered a highly prevalent facultative plant-parasitic nematode and has a significant impact on various economically important crops globally. Due to the lack of knowledge on the efficacy of various management techniques, A. besseyi is still challenging to control in the open field. The present investigation successfully shed light on some significant new points, including the following: (1) A. besseyi was confirmed inside all soybean tissues—including roots, stems, leaves, and seeds—indicating its endoparasitic nature and its strong ability to reach the upper foliar system where it causes green stem and foliar retention syndrome (GSFR) symptoms; (2) inoculated plants exhibited reduced vegetative growth parameters, as non-inoculated control soybean plants showed higher values of plant height (PH), fresh root weight (FRW), and fresh shoot weight (FSW) compared to inoculated plants; (3) Yudou 29 was identified as highly resistant to A. besseyi, as results from the resistance screening assay among different Chinese soybean cultivars confirmed its strong resistance under natural field infestation conditions; and (4) soybean seeds may act as inoculum sources of A. besseyi, highlighting the need to develop more effective control measures to prevent or limit nematode dissemination through seed transmission. Full article

In this study, we established a mouse colitis model using DSS to investigate the impact of curcumin on gut injury, the intestinal microbiota, and fecal metabolites. The findings indicated that curcumin effectively mitigated weight loss and colon shortening caused by colitis, enhanced the expression of anti-inflammatory factor IL-10 mRNA (p < 0.05), and suppressed the expression of pro-inflammatory factors (IL-1β, IL-6, and TNF-α mRNA; p < 0.05). 16S rDNA sequencing analysis showed that in the CUR group, compared to the NC and DSS groups, the abundances of Bacteroides, Lachnospiraceae NK4A136, and Ruminococcaceae UGC 014 significantly increased, while that of Lactobacillus markedly decreased. Additionally, compared with the DSS group, the CUR group demonstrated a significant decrease in levels of metabolites associated with nucleic acid and fat metabolism, including xanthosine, isocitric acid, and D-xylose. Conversely, levels of metabolites of curcumin, such as demethoxycurcumin and tetrahydrocurcumin, were significantly elevated in the CUR group. Curcumin appears to offer protection against mouse colitis by potentially enhancing the composition of the gut microbiota and regulating metabolic and inflammatory processes through its metabolites. Full article

Kallmann syndrome (KS) is a form of hypogonadotropic hypogonadism (HH) characterized by gonadotropin-releasing hormone (GnRH) deficiency and anosmia due to defective neuronal migration. While traditionally considered irreversible, cases of spontaneous improvement of HH have been reported, suggesting residual GnRH neuronal function in some individuals. We present a case of a 29-year-old man with KS who exhibited spontaneous recovery of endogenous testosterone production following the cessation of long-term androgen therapy without the use of alternative hormonal agents. After ceasing testosterone therapy for several months, the patient’s total testosterone levels normalized (407–424 ng/dL), accompanied by increased secondary sexual characteristics, stable gonadotropin levels, and normal testicular volume. Persistent anosmia was noted, suggesting that restoration of reproductive endocrine function can occur independently of olfactory recovery. Genetic testing identified heterozygous mutations in PCSK1 and HS6ST1, genes implicated in GnRH regulation and KS pathogenesis. This case highlights the potential role of genetic variation in spontaneous HH improvement and underscores the need for individualized management strategies, including periodic reassessment of gonadal function and fertility potential. Further research is needed to elucidate the mechanisms driving spontaneous HH improvement, identify predictive biomarkers of reversibility, and explore therapeutic strategies that may promote endogenous GnRH activity in select patients with KS. Full article

In this study we searched for correlations between polymorphic variants that determine sex hormone-binding globulin concentration (SHBG_con) and uterine fibroids (UFs). The work was performed on a sample of 1542 women (569 with UFs and 973 without UFs [control]), from whom we obtained experimental data on the distribution of nine single-nucleotide polymorphisms (SNPs) affecting the SHBG_con (data confirmed in genome-wide association studies [GWASs]). When searching for associations with UFs, both the independent effects of SNPs and the effects of their SNP–SNP interactions (SNP-SNP_ints) were taken into account during the “deep study” of the functionality of seven important UF loci and 115 strongly linked [r² ≥ 0.80] variants (an in silico methodology was used). As the results show, two SHBG_con-related SNPs correlated with UF risk: rs3779195 [T/A] BAIAP2L1 (OR_AA = 0.38; 95%CI_AA = 0.20–0.91; p_perm(AA) = 0.023) and rs440837 [A/G] ZBTB10 (OR_GG = 1.93; 95%CI_GG = 1.17–3.14; p_perm(GG) = 0.010). At the same time, seven SHBG_con-related SNPs interacting with each other (four models of such SNP-SNP_ints [p_perm ≤ 0.01)] were found to influence UF risk. These SHBG_con-related SNPs, determining susceptibility to UF, showed strong functional relevance and were involved in pathways of gene transcription regulation, interactions with hormone ligand-binding receptors, the content control of SHBG, testosterone, liver enzymes, lipids, etc. This study’s results demonstrate the effect of significant SHBG_con-related genetic determinants of UF risk. Full article

Background: Blood pressure (BP) variability has been increasingly recognized as a predictor of cardiovascular and renal outcomes. However, the relevance of specific dynamic indices such as the maximum slope of systolic blood pressure (max SBP slope), derived through partial Fourier series modeling, in relation to early renal damage remains underexplored. Methods: A total of 389 patients with essential hypertension were enrolled and stratified according to the estimated glomerular filtration rate (eGFR) ≥ or <90 mL/min/1.73 m² and the presence of subclinical renal damage, defined by elevated urinary albumin excretion (AER) and/or reduced eGFR. All participants underwent clinical and biochemical evaluation, as well as 24-h ambulatory blood pressure monitoring (ABPM), including advanced hemodynamic analysis using Fourier-based modeling. Results: Patients with eGFR < 90 mL/min/1.73 m² were older and exhibited higher waist circumference, uricemia, albuminuria, and systolic BP values, including the elevated max SBP slope (12.8 vs. 10.8 mmHg/h, p = 0.028). Subclinical renal damage was associated with older age; male sex; smoking; and higher levels of uricemia, clinical, and ambulatory BP, and the max SBP slope (14.2 vs. 10.7 mmHg/h, p = 0.007). The max SBP slope positively correlated with AER (r = 0.215, p < 0.001) and inversely with eGFR (r = −0.153, p = 0.002). In multivariate linear regression, the max SBP slope remained independently associated with AER (β = 0.220, p < 0.001), along with mean 24-h SBP, male sex, and the day–night SBP percentage dip. Logistic regression confirmed these associations with subclinical renal damage (max SBP slope OR: 1.536; 95% CI: 1.241–2.004; p = 0.001). Conclusions: The max SBP slope, a dynamic index of BP derived via Fourier analysis, is independently associated with markers of subclinical renal damage in hypertensive patients. This suggests that incorporating such advanced metrics into ABPM evaluation may improve early risk stratification and help identify individuals at greater risk of renal impairment, even in the absence of overt kidney disease. Full article

Cellulite is a widespread aesthetical dermatological condition affecting a significant proportion of postpubertal women, characterized by dimpled skin, primarily on the thighs, buttocks, and hips, which has an important psychological impact. Cellulite, also called lipodystrophy or oedematosclerotic panniculitis, causes an aesthetic change in the skin that affects the epidermis, dermis, hypodermis and subcutaneous fat in different ways. The aim of the present prospective study research was to evaluate the efficacy of electromagnetic field and negative pressure in the treatment of cellulite. Methods: A total of 35 women with an average age of 40, ranging from 18 to 50 (mean 32.2 ± 7.48), with a body mass index between 18.5 and 26.9 (mean 22 ± 3.01), were enrolled in this study. The degree of cellulite of the patients was assessed clinically using the Cellulite Severity Scale (CSS) and Nürnberger–Müller classification. All patients received one session per week for a total 12 treatment sessions with Bi-one^® LifeTouchTherapy medical device (Expo Italia Srl—Florence—Italy), which generates a combination of vacuum and electromagnetic fields (V-EMF). Total treatment time was approximately 20–30 min per patient. The GAIS score, Cellulite Severity Scale (CSS) and Nürnberger–Müller classification for cellulite was evaluated 1 month after the 12 treatments with LifeTouchTherapy. Results: A statistical difference was recorded in cellulite improvement by visual analog scale (VAS) and global aesthetic improvement scale (GAIS). Conclusions: The results of the present prospective clinical study show the efficacy and safety of Bi-one^® LifeTouchTherapy in the treatment of cellulite. Electromagnetic fields combined with negative pressure therapy promote tissue regeneration and reduce fibrosis, which results in visible cosmetic improvements of cellulite. Full article

Background: Brain-derived neurotrophic factor (BDNF) plays a pivotal role in neuroplasticity and cognitive development. While exercise has been shown to modulate BDNF levels in adults, evidence in children remains limited and heterogeneous. Methods: A systematic review was conducted following PRISMA guidelines to examine randomized controlled trials investigating exercise effects on BDNF in children aged 5–12 years. The databases searched included FECYT, PubMed, SPORTDiscus, ProQuest Central, SCOPUS, and Cochrane Library through June 2025. Study quality was assessed using the PEDro scale. Results: Five randomized controlled trials (N = 385 participants) met inclusion criteria. Two studies (40%) demonstrated significant BDNF increases following exercise interventions. Successful interventions were characterized by neuromotor activities or martial arts programs, training frequencies ≥ 3 sessions/week, durations ≥ 12 weeks, and healthy participant populations. Methodological quality was mostly fair, with four studies rated as fair and one as good. Conclusions: Structured physical exercise may enhance BDNF levels in healthy children, with neuromotor activities and martial arts showing particular promise. However, children with overweight/obesity may require modified intervention approaches. The evidence supports the implementation of cognitively engaging physical activities in educational settings to optimize brain health during critical developmental periods, though larger standardized trials are needed to strengthen these preliminary findings. Full article

This comment focuses on the contribution of experimental brain ischemia to the overwhelming incidence of Alzheimer’s disease in women as presented by Lohkamp et al. in Life 2025, 15, 333. The authors showed that in Alzheimer’s disease and ischemic stroke there are sex-dependent adaptations in the form of cross-links and vice versa. It was emphasized that the high longevity of women in itself does not explain the mechanisms underlying the biological differences between the sexes causing a female predominance in the development of Alzheimer’s disease. Differences were demonstrated between males and females: female APP/PS1 mice had greater amyloid deposition, hyperactivity, lower body weight, and reduced cerebral blood flow, as well as less neuroinflammation, which the authors suggest may have potential neuroprotection. It should be noted that some of the information presented in the article by Lohkamp et al. raises more questions than answers. Therefore, future studies should consider, for example, studies using single-cell technologies that can provide insight into the timing and sequence of cellular dysfunctions across sexes and analyze the continuity of changes over time, starting from short-term observations of a few days and ending with long-term observations of a year or more, to assess the continuity and differentiation of changes. Full article

The present study aimed to investigate the electrophysiological correlates of face-identity recognition in newborn infants immediately after birth. Electroencephalographic acquisition was continuously recorded in 23 newborn infants (3 < age < 24 h of life) during the following visual task: presentation of a woman’s face for 60 s (“known face”); random presentation of 50 known faces, 50 novel women’s faces, and 50 chessboards (for 2 s each). The final sample included in ERP analyses was composed of 11 newborn infants (male/female: 6/5; age: 5 h 16′ ± 3 h 51′). A greater negative amplitude of the N290 and smaller P400 and LC2 were found in response to the known face compared with the novel one in the left hemisphere. A shorter N290 latency was detected during the known face presentation compared with the novel one, and a longer latency of the same component was observed during novel face presentation compared with the chessboard. These findings suggest that newborns process a face differently from an object at birth and that they can discriminate a new face from a familiar one previously viewed for one minute. Full article

This study aimed to assess skeletal and upper airway modifications induced by the Twin Block appliance in patients with Class II malocclusion due to mandibular retrusion, using two-dimensional imaging techniques. A total of 11 patients (6 males, 5 females) were included and stratified into two groups (Pre-Peak and Peak) based on skeletal maturity evaluated through the cervical vertebral maturation (CVM) method. Lateral cephalometric radiographs were obtained at the beginning (T0) and end (T1) of treatment and analyzed using DeltaDent software. The appliance was worn full-time, except during meals and oral hygiene procedures, with monthly follow-ups. Significant changes were observed between T0 and T1 across the sample. Comparison between groups revealed statistically significant differences only in the H-C3a1 and vertical height (th) parameters (p < 0.05). In conclusion, the Twin Block appliance proved effective in enhancing mandibular and dental positioning, while also exerting a favorable influence on upper airway development. Full article

Investigations of endogenous plant circular RNAs (circRNAs) in several plant species have revealed changes in their circular RNA profiles in response to biotic and abiotic stresses. Recently, circRNAs have emerged as critical regulators of gene expression. The destructive impacts on agriculture due to plant viral infections necessitate better discernment of the involvement of plant circRNAs during viral infection. However, few such studies have been conducted hitherto. Sobemoviruses cause great economic impacts on important crops such as rice, turnip, alfalfa, and wheat. Our current study investigates the dynamics of plant circRNA profiles in the host Arabidopsis thaliana (A. thaliana) during infections with the sobemoviruses Turnip rosette virus (TRoV) and Rice yellow mottle virus (RYMV), as well as the small circular satellite RNA of the Lucerne transient streak virus (scLTSV), focusing on circRNA dysregulation in the host plants and its potential implications in triggering plant cellular defense responses. Towards this, two rounds of deep sequencing were conducted on the RNA samples obtained from infected and uninfected plants followed by the analysis of circular RNA profiles using RNA-seq and extensive bioinformatic analyses. We identified 760 circRNAs, predominantly encoded in exonic regions and enriched in the chloroplast chromosome, suggesting them as key sites for circRNA generation during viral stress. Gene ontology (GO) analysis indicated that these circRNAs are mostly associated with plant development and protein binding, potentially influencing the expression of their host genes. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed photosynthesis as the most affected pathway. Interestingly, the non-coding exogenous scLTSV specifically induced several circRNAs, some of which contain open reading frames (ORFs) capable of encoding proteins. Our biochemical assays demonstrated that transgenic expression of scLTSV in A. thaliana enhanced resistance to TRoV, suggesting a novel strategy for improving plant viral resistance. Our results highlight the complexity of circRNA dynamics in plant–virus interactions and offer novel insights into potential circRNA-based strategies for enhancing plant disease resistance by modulating the differential expression of circRNAs. Full article

Obesity-related low-grade inflammation is a significant factor responsible for the development of metabolic syndrome and chronic diseases, which can begin even in early childhood. Recently, there has been growing interest in the impact of vitamin D3 supplementation on inflammatory markers in overweight and obese individuals; however, findings remain inconsistent. Therefore, we aimed to conduct a systematic review to assess the effects of vitamin D3 supplementation on inflammatory markers in overweight and obese children and adolescents, focused exclusively on the analysis of randomized controlled trials (RCTs) identified by searching PubMed, EMBASE, and Cochrane Library. The results of this study were synthesized and reported following the PRISMA statement. A total of 294 citations were identified through electronic literature searches, of which two RCTs were finally included in our systematic review. We found that vitamin D3 supplementation did not affect the changes in C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), but led to a decrease in leptin levels. The small number of studies meeting the inclusion criteria for our systematic review limits the value of the presented results, but also indicates the need for in-depth research on this topic. Full article

Due to advances in molecular technologies and the expanding knowledge of biomarkers, their use in patient screening, diagnosis, prognosis, and targeted therapy is continuously increasing. Biomarker characteristics play a crucial role across all areas of medical research/practice. Biomarkers often reflect changes in the biochemical composition of biofluids, which can be qualitatively and quantitatively analyzed using methods such as high-performance liquid chromatography (HPLC) at various stages of clinical intervention. This study focuses on establishing physiological reference ranges for selected biochemical and metabolomic indicators by analyzing blood serum samples from domestic sheep. A total of sixty samples are examined using standard biochemical assays and HPLC, resulting in the determination of experimental reference values for twenty-one biochemical and eight metabolomic parameters. Reliable and reproducible preclinical testing is essential before any diagnostic method can be introduced into clinical use. A thorough understanding of the safety and efficacy of such methods in animal models is a prerequisite for initiating human trials. Species selection and the definition of physiological biomarker ranges are therefore critical components in the development of effective preclinical protocols. This work contributes to the foundation needed for further clinical testing by establishing reference values for relevant biomarkers in a commonly used animal model. Full article

Introduction/Objectives: Osteoarthritis (OA) is a chronic systemic disease that affects the entire array of joint structures. It is one of the most common chronic, socially significant diseases, associated with a decline in the quality of life of patients and constantly increasing the cost of treatment. Clinical trial outcomes are largely inconclusive, and OA remains one of the few musculoskeletal diseases without an established disease-modifying therapy. One potential explanation is the use of ineffective tools for OA classification, patient stratification, and the assessment of disease progression. There is growing interest in musculoskeletal ultrasonography (MSK US), as it enables the dynamic visualization of the examined structures and gives information about both inflammatory and structural changes that have occurred. Determining the leading ultrasound phenotype, which depends on the most damaged tissue at a given time (bone, cartilage, synovial membrane, joint capsule, ligaments, tendons, menisci, etc.), can rationalize therapy use by selecting patients more suitable for specific treatments. This article aims to evaluate and summarize the potential of MSK US in the process of determining the clinical phenotype of OA and to emphasize the importance of this imaging modality in evaluating further therapeutic strategies. Method: A single-center prospective study conducted in the period of September 2023–June 2024 enrolled 259 consecutive patients with proven OA. The statistical program Minitab version 22.2.1 (2025) was used to analyze the data. The predominant and secondary phenotypes were tabulated for each OA localization and were presented numerically and as relative proportions (%). The rate of the most frequently occurring phenotypes was compared against that of the less frequent ones through paired z-tests. The initially acceptable type I error was set at 5%; it was further adjusted for the number of comparisons (Bonferroni). Results: The most frequent and predominant US phenotype for patients with knee OA was intra-articular effusion (n = 47, 37.90%). It was significantly higher compared to the rest of the US phenotypes: synovial proliferation (n = 22, 17.70%; p < 0.001), cartilage destruction (n = 26, 21%; p = 0.001), altered subchondral bone (n = 8, 6.50%; p < 0.001), extra-articular soft tissue changes (n = 12, 9.70%; p < 0.001), crystal deposits (n = 6, 4.8%; p < 0.001), and post-traumatic (n = 3, 2.40%; p < 0.001). The most common US phenotype for hip OA was altered subchondral bone (n = 32, 47.1%), with significant differences from intra-articular effusion (n = 12, 17.60%; p = 0.001), synovial proliferation (n = 5, 7.40; p = 0.001), cartilage destruction (n = 12, 17.60%; p = 0.001), extra-articular soft tissue changes (n = 3, 4.40%; p = 0.001), crystal deposits (n = 3, 4.40%; p = 0.001), and post-traumatic (n = 0). Altered subchondral bone was also the leading US phenotype for hand OA (n = 31, 55.40%), with significant differences compared to intra-articular effusion (n = 1, 1.80%; p < 0.001), synovial proliferation (n = 7, 12.50%; p < 0.001), cartilage destruction (n = 11, 19.60%; p < 0.001), extra-articular soft tissue changes (n = 2, 3.60%; p < 0.001), crystal deposits (n = 3, 5.40%; p < 0.001), and post-traumatic (n = 1, 1.80%, p < 0.001). For shoulder OA, extra-articular soft tissue changes were the most frequent (n = 8, 46.20%), followed by post-traumatic (n = 4, 30.70%), as the rate of both phenotypes was significantly higher compared to that of intra-articular effusion (n = 0), synovial proliferation (n = 0), cartilage destruction (n = 1, 7.70%; p = 0.003), and crystal deposits (n = 0). Conclusions: The therapeutic approach for OA is a dynamic and intricate process, for which the type of affected joint and the underlying pathogenetic mechanism at a specific stage of the disease’s evolution is essential. MSK US is one of the options for the clinical phenotyping of OA. Some of the suggested ultrasound subtypes may serve as the rationale for selecting a particular treatment. Full article

S-nitrosoglutathione (GSNO), a promising S-nitrosothiol, has been recognized for its ability to modulate vascular tone through its vasodilatory, antiplatelet, and antiproliferative effects. However, data on its vasodilatory effects in human vessels remain limited, and its mechanisms of action have yet to be fully elucidated. In this study, we aimed to investigate the vasorelaxant effect of GSNO and its underlying mechanisms, with particular focus on the soluble guanylate cyclase (sGC)/nitric oxide (NO) pathway and potassium channels in isolated human saphenous veins (SVs) obtained from patients undergoing coronary artery bypass grafting (CABG). GSNO (10⁻⁸–10⁻⁴ M) produced concentration-dependent relaxations in SV rings precontracted with phenylephrine. These relaxations were unaffected by NO synthase inhibition with L-NAME (10⁻⁴ M, 30 min) or NO scavenging with PTIO (10⁻⁴ M, 30 min), but were significantly reduced by the sGC inhibitor, ODQ (10⁻⁵ M, 30 min). Inhibition of ATP-sensitive (glibenclamid; 10⁻⁵ M, 30 min.), high-conductance Ca²⁺-activated (charybdotoxin; 10⁻⁷ M, 30 min), small-conductance Ca²⁺-activated (apamin; 10⁻⁶ M, 30 min), or voltage-dependent (4-aminopyridine; 10⁻³ M, 30 min) potassium channels did not alter the maximum relaxant responses to GSNO. Furthermore, pretreatment with GSNO (10⁻⁴ M, 30 min) significantly attenuated both the contractile response and sensitivity to phenylephrine. Collectively, these findings demonstrate that GSNO exerts acute vasorelaxant and modulatory effects in human SV primarily via cGMP-dependent mechanisms, highlighting its potential as a local therapeutic agent for preventing graft spasm in CABG. Full article

Traumatic liver injury remains a significant contributor to trauma-related morbidity and mortality worldwide. In Saudi Arabia, motor vehicle accidents (MVAs) are the predominant mechanism of injury, particularly among young adults. This study aimed to evaluate the clinical characteristics, management strategies, and outcomes of patients with liver trauma over a ten-year period at a tertiary academic level-one trauma center. A retrospective cohort study was conducted from January 2015 to December 2024. All adult patients (aged 18–65 years) who sustained blunt or penetrating liver injuries and underwent a pan-CT trauma survey were included. Demographic data, Injury Severity Scores (ISSs), imaging timelines, management approach, and clinical outcomes were analyzed. Statistical analysis was performed using JASP software with a significance threshold set at p < 0.05. A total of 111 patients were included, with a mean age of 33 ± 12.4 years; 78.1% were male. MVAs were the leading cause of injury (75.7%). Most patients (80.2%) had low-grade liver injuries and received non-operative management (NOM), with a high NOM success rate of 94.5%. The median time to CT was 55 ± 64 min, and the mean time to operative or IR intervention was 159.9 ± 78.8 min. Complications occurred in 32.4% of patients, with ventilator-associated pneumonia (19.8%) being most common. The overall mortality was 6.3%. Multivariate analysis revealed that shorter time to CT significantly reduced mortality risk (OR = 0.5, p < 0.05), while a positive e-FAST result was strongly associated with increased mortality (OR = 3.3, p < 0.05). Higher ISSs correlated with longer monitored unit stays (ρ = 0.3, p = 0.0014). Traumatic liver injuries in this cohort were predominantly low-grade and effectively managed conservatively, with favorable outcomes. However, delays in imaging and operative intervention were observed, underscoring the requirement for streamlined trauma workflows. These findings highlight the requirement for continuous trauma system improvement, including protocol optimization and timely access to imaging and surgical intervention. Full article

Pulmonary hypertension (PH) encompasses a group of conditions characterized by elevated pulmonary arterial pressure, with pulmonary arterial hypertension (PAH) representing a distinct and severe subset. This review provides a comprehensive overview of the current classification system, highlighting the five clinical groups of PH and the specific hemodynamic criteria defining PAH. We discuss the complex pathophysiological mechanisms underlying PAH, including vascular remodeling, endothelial dysfunction, and genetic predisposition. Advances in diagnostic approaches are explored. Current treatment strategies targeting key molecular pathways such as endothelin, nitric oxide, and prostacyclin are reviewed alongside novel and investigational therapies. Prognostic indicators and risk stratification tools are evaluated to guide clinical management. Finally, we underscore the critical role of expert centers in accurate diagnosis, multidisciplinary care, and enrollment in clinical trials, which collectively improve patient outcomes in this challenging disease spectrum. Full article

Background: While Asia contributes 44.3% of traumatic brain injuries (TBI) worldwide, data regarding Asian TBI inpatient rehabilitation length of stay (RLOS) is scarce. A retrospective cohort study was conducted to determine correlates of inpatient RLOS (days) and prolonged RLOS >30 days (PRLOS > 30). (2) Methods: Data extraction of discharged inpatient records was performed from 2018 to 2024. Dependent variables included RLOS (days) and PRLOS > 30. Independent variables included demographic characteristics, TBI severity (emergency-room Glasgow Coma Scale-GCS), admission/discharge Functional Independence Measure (FIM), intra-rehabilitation complications, post-traumatic amnesia (PTA) duration, and discharge placement. (3) Results: Altogether, 289 data sets were analysed, median (IQR) age, 64 (28) years, 78.9% (228/289) males, and 79.6% (230/289) Chinese. Median (IQR) RLOS was 28 (21) days, with PRLOS >30 at 39.8% (115/289); RLOS of 44 (19.5) days. PRLOS > 30 was significantly associated with PTA duration >28 days (OR 4.01, 95% CI 1.90–8.45, p < 0.001), admission FIM ≤ 40/126 (OR 4.71, 95% CI 2.32–9.59, p < 0.001), delayed neurosurgical complications (OR 4.74, 95% CI 1.28–17.6, p = 0.02) and discharge to non-home destination (OR 2.75. 95% CI 1.12–6.76, p = 0.03). (4) Conclusion: PRLOS >30 was significantly associated with longer PTA > 4 weeks, lower admission FIM score, delayed neurosurgical complications, and discharge to a nursing home. Full article

Accurate detection of fractures in X-ray images is important to initiate appropriate medical treatment in time—in this study, an advanced combined attention CNN model with multiple attention mechanisms was developed to improve fracture detection by deeply representing features. Specifically, our model incorporates squeeze blocks and convolutional block attention module (CBAM) blocks to improve the model’s ability to focus on relevant features in X-ray images. Using computed tomography X-ray images, this study assesses the diagnostic efficacy of the artificial intelligence (AI) model before and after optimization and compares its performance in detecting fractures or not. The training and evaluation dataset consists of fractured and non-fractured X-rays from various anatomical locations, including the hips, knees, lumbar region, lower limb, and upper limb. This gives an extremely high training accuracy of 99.98 and a validation accuracy 96.72. The attention-based CNN thus showcases its role in medical image analysis. This aspect further complements a point we highlighted through our research to establish the role of attention in CNN architecture-based models to achieve the desired score for fracture in a medical image, allowing the model to generalize. This study represents the first steps to improve fracture detection automatically. It also brings solid support to doctors addressing the continued time to examination, which also increases accuracy in diagnosing fractures, improving patients’ outcomes significantly. Full article

Chronic coronary syndrome (CCS) and atrial fibrillation (AF) are prevalent cardiovascular conditions that share numerous risk factors and pathophysiological mechanisms. While clinical scores commonly used in AF—such as CHA₂DS₂VA (which includes congestive heart failure, hypertension, age ≥ 75, diabetes, stroke/TIA, vascular disease, and age 65–74), HAS-BLED (which incorporates hypertension, abnormal renal/liver function, stroke, bleeding history, labile INR, elderly age, and drug/alcohol use), and C₂HEST (incorporating coronary artery disease, COPD, hypertension, elderly age ≥ 75, systolic heart failure, and thyroid disease)—are traditionally applied to rhythm or bleeding risk prediction, their value in estimating the angiographic severity of coronary artery disease (CAD) remains underexplored. We conducted a prospective, single-center study including 131 patients with suspected stable CAD referred for coronary angiography, stratified according to coronary angiographic findings into two groups: significant coronary stenosis (S-CCS) and non-significant coronary stenosis (N-CCS). At admission, AF-related scores (CHA₂DS₂, CHA₂DS₂VA, CHA₂DS₂VA-HSF, CHA₂DS₂VA-RAF, CHA₂DS₂VA-LAF, HAS-BLED, C₂HEST, and HATCH) were calculated. CAD severity was subsequently assessed using the SYNTAX and Gensini scores. Statistical comparisons and Pearson correlation analyses were performed to evaluate the association between clinical risk scores and angiographic findings. Patients in the S-CCS group had significantly higher scores in CHA₂DS₂VA (4.09 ± 1.656 vs. 3.20 ± 1.338, p = 0.002), HAS-BLED (1.98 ± 0.760 vs. 1.36 ± 0.835, p < 0.001), CHA₂DS₂VA-HSF (6.00 ± 1.854 vs. 5.26 ± 1.712, p = 0.021), and C₂HEST (3.49 ± 1.501 vs. 2.55 ± 1.279, p < 0.001). Multivariate logistic regression identified HAS-BLED and C₂HEST as independent predictors of significant coronary lesions. A threshold value of HAS-BLED ≥ 1.5 and C₂HEST ≥ 3.5 demonstrated moderate discriminative ability (AUC = 0.694 and 0.682, respectively), with acceptable sensitivity and specificity. These scores also demonstrated moderate to strong correlations with both Gensini and SYNTAX scores. AF-related clinical scores, especially HAS-BLED and C₂HEST, may serve as practical and accessible tools for early CAD risk stratification in patients with suspected CCS. Their application in clinical practice may serve as supplementary triage tools to help prioritize patients for further diagnostic evaluation, but they are not intended to replace standard imaging or testing. Full article

Background: Endometrial cancer (EC) is the most common gynecological malignancy, increasingly affecting premenopausal women. While hysterectomy is the standard treatment, it eliminates reproductive potential, highlighting the need for effective fertility-sparing alternatives. Current ESHRE/ESGO/ESGE guidelines recommend progestin-based therapies, often with hysteroscopic resection. However, these are based on limited pharmacological options and moderate to low-quality evidence. Novel and combination therapies have shown promise but remain absent from current clinical guidelines. This review aims to evaluate the efficacy and safety of fertility-preserving treatments for early-stage EC, emphasizing the need to update current strategies based on emerging data. Methods: A systematic review and meta-analysis will follow PRISMA guidelines and the Cochrane Handbook. Eligible studies, including randomized and non-randomized designs, will assess fertility-preserving treatments for early-stage EC. Data will be extracted on complete response, recurrence, and long-term fertility outcomes. The GRADE system will assess evidence certainty. Risk of bias will be evaluated using RoB 2 for RCTs and ROBINS-I for non-randomized studies. Meta-analysis will be performed if sufficient data are available. Conclusions: This review will provide a comprehensive analysis of fertility-sparing treatments for early-stage EC, support personalized strategies, identify evidence gaps, and guide future research. Trial registration—Prospero: CRD420251032161. Full article

A key aspect driving advancements in machine learning applications in medicine is the availability of publicly accessible datasets. Evidently, there are studies conducted in the past with promising results, but they are not reproducible due to the fact that the data used are closed or proprietary or the authors were not able to publish them. The current study aims to narrow this gap for researchers who focus on image recognition tasks in microbiology, specifically in fungal identification and classification. An open database named OpenFungi is made available in this work; it contains high-quality images of macroscopic and microscopic fungal genera. The fungal cultures were grown from food products such as green leaf spices and cereals. The quality of the dataset is demonstrated by solving a classification problem with a simple convolutional neural network. A thorough experimental analysis was conducted, where six performance metrics were measured in three distinct validation scenarios. The results obtained demonstrate that in the fungal species classification task, the model achieved an overall accuracy of 99.79%, a true-positive rate of 99.55%, a true-negative rate of 99.96%, and an F1 score of 99.63% on the macroscopic dataset. On the microscopic dataset, the model reached a 97.82% accuracy, a 94.89% true-positive rate, a 99.19% true-negative rate, and a 95.20% F1 score. The results also reveal that the model maintains promising performance even when trained on smaller datasets, highlighting its robustness and generalization capabilities. Full article

Acute Rheumatic Fever (ARF) is more common in children in the developing world. The current incidence in the United Kingdom is reported to be less than 1 in 100,000 children. It is, however, rare in the developed world, particularly in the adult Caucasian population. We present a case of ARF in a 39-year-old Caucasian female who needed multiple hospital admissions before the ARF diagnosis was made. A comprehensive, up-to-date literature review of ARF in Caucasians is lacking. Therefore, a systematic literature review (SLR) of Medline, PubMed, and Google Scholar was conducted to investigate the characteristics, management, and prognostic outcomes of new cases of ARF among Caucasians. A total of 10 cases were reported from six countries between 1990 and 2022. The mean age of patients was 33.2 (range 18–41), and most were females (6, 60%). The most common presenting symptoms were fever, arthralgia, and malaise. All patients met the modified Jones criteria for ARF diagnosis. All patients received antibiotics, with only one patient requiring corticosteroids. Two patients developed rheumatic heart disease (RHD), and none died as a result of ARF. This case-based literature review underscores the critical importance of a high index of clinical suspicion in promptly diagnosing ARF to mitigate long-term sequelae of RHD. Full article

Background: The global impact of the COVID-19 pandemic has significantly influenced elderly functionality, particularly in terms of balance, gait, and independence in daily activities. This study sought to evaluate how these aspects have changed over the course of the health crisis. Methods: We employed the Tinetti scale for assessing balance and gait, and the Barthel Index for measuring functional independence, conducting a comparative analysis of scores before and after the onset of the pandemic in a sample of elderly individuals. Results: Our findings indicated an increase in Tinetti scores, suggesting some improvement in balance and mobility, albeit with marked variability across participants. On the other hand, Barthel scores showed a significant decline, pointing to a reduction in functional independence. Conclusions: These results suggest that the impact of COVID-19 on elderly functionality is not uniform, highlighting the need for personalized rehabilitation strategies. Such strategies should not only focus on physical recovery but also consider the psychological and social repercussions of the pandemic to fully address the diverse needs of this vulnerable population. Full article

The main challenge after engraftment of human tissues to mice is the development of graft-versus-host disease. It often occurs in an acute form, which reduces the time frame for observations. This is especially important to take into account when planning long-term studies of chronic diseases such as HIV infection. In addition, in mice, even with a similar genotype but different origin, the interaction between the graft and the recipient’s organism can manifest itself differently. We engrafted human immune cells in three different concentrations into immunodeficient NOD/Shi-Prkdc^scid Il2rg^em1/Cyagen mice. Then, the initial points of development of a severe graft-versus-host reaction and the maximum possible time window for humane observation were determined. The study included regular complete blood count and the monitoring of the dynamics of the concentration of human cells in the blood of mice. In addition, the effect of grafts on the activation of the recipient’s immune system was assessed. Finally, necropsy and histological and immunohistochemical examinations of the organs were performed to determine the localization of human cells. In this way, critical factors determining the success of human immune system reconstitution in mice were identified. Full article

The main goal of purebred cat breeding is to produce healthy offspring while maintaining breed purity. Pedigree cat breeders are affiliated with international federations that enforce similar breeding regulations, which helps prevent the overexploitation of cats in breeding. The minimum age for allowing a cat to breed is at least 10 months. This study aimed to analyze the breeding performance of three cat breeds: Maine Coon (MCO), British Shorthair (BSH), and Devon Rex (DRX). These breeds are classified as late-maturing (MCO), medium-late maturing (BSH), and early-maturing (DRX). The analysis was based on pedigree data obtained from the Polish Felinological Association, which operates under the auspices of the World Cat Federation. In total, data from 1016 litters (453 MCO, 453 BSH, and 110 DRX) were analyzed. Breeds differed significantly in age at first birth (p = 0.041), mean interval between litters (p < 0.01), and mean number of kittens per litter (p < 0.01). Breed effects were also noted for the mean interval between births (p < 0.01), mean number of kittens per litter (p < 0.01), and the total number of kittens sired by the mother (p = 0.007). Within each breed, differences were found in the sex ratio of litters, with a predominance of males in DRX (p = 0.049), MCO (p = 0.003), and overall breeds (p = 0.036). In contrast, the BSH breed showed no significant difference in the sex ratio of litters (p = 0.455). In both the MCO and DRX breeds, the lowest average interval between litters was observed in females that gave birth to their first litter early compared to those that gave birth later. The total number of kittens raised by the mother was highest in the MCO breed (p ≤ 0.05), while the shortest litter spacing was found in the DRX breed (p ≤ 0.05). Full article

The secondary sex ratio (SSR), defined as the ratio of male to female births in a population, has long been a subject of scientific inquiry due to its potential as a health indicator. The interplay between catastrophic events and the delicate balance of male and female births presents a nuanced and compelling study area. Natural disasters, such as earthquakes, hurricanes, floods, and volcanic eruptions, have been known to disrupt ecosystems and human populations, leading to both short-term and long-term consequences. Studies have suggested a potential influence of these disasters on the SSR, with varying degrees of impact observed across different regions and disaster types. Similarly, nuclear accidents, such as the infamous Chernobyl disaster, have sparked interest in their potential effects on human health and development. The release of radioactive materials into the environment can have far-reaching consequences, including impacts on reproductive outcomes. Through a rigorous examination of the existing literature, the present review aims to synthesize current knowledge on the impacts of natural disasters and nuclear accidents on the SSR and unravel the mechanisms that explain SSR fluctuations. By shedding light on the diverse influences shaping the SSR, this narrative review contributes to a deeper appreciation of the intricate interplay between environmental, biological, and societal factors that determines the SSR, calling for targeted strategies to mitigate potential adverse effects on sex ratios in the aftermath of such events. Full article

Theobroma cacao L. (cocoa) pod husk, a byproduct of the chocolate industry, has potential for commercial applications due to its bioactive compounds. This study aimed to determine the phytochemical composition, biological activity, and clinical efficacy of a standardized extract. This study compared 80% ethanol (CE) and 80% ethanol acidified (CEA) as extraction solvents. The result indicated that CEA yielded higher total phenolic content (170.98 ± 7.41 mg GAE/g extract) and total flavonoid content (3.91 ± 0.27 mg QE/g extract) than CE. Liquid chromatography–tandem mass spectrometry (LC/MS/MS) identified various phenolic and flavonoid compounds. CEA demonstrated stronger anti-oxidant (IC₅₀ = 5.83 ± 0.11 μg/mL in the DPPH assay and 234.17 ± 4.01 mg AAE/g extract in the FRAP assay) compared to CE. Additionally, CEA exhibited anti-tyrosinase (IC₅₀ = 9.51 ± 0.01 mg/mL), anti-glycation (IC₅₀ = 62.32 ± 0.18 µg/mL), and anti-collagenase (IC₅₀ = 0.43 ± 0.01 mg/mL), nitric oxide (NO) production inhibitory (IC₅₀ = 62.68 μg/mL) activities, without causing toxicity to cells. A formulated lotion containing CEA (0.01–1.0% w/w) demonstrated stability over six heating–cooling cycles. A clinical study with 30 volunteers showed no skin irritation. The 1.0% w/w formulation (F4) improved skin hydration (+52.48%), reduced transepidermal water loss (−7.73%), and decreased melanin index (−9.10%) after 4 weeks of application. These findings suggest cocoa pod husk extract as a promising active ingredient for skin hydrating and lightening formulation. Nevertheless, further long-term studies are necessary to evaluate its efficacy in anti-aging treatments. Full article