Medical Sciences

Background: Steroidal glucocorticoid and gestagenic drugs and cold plasma-treated solutions (PTSs) are known to exert anti-inflammatory effects by influencing the production of a number of cytokines. The aim of this work was to test their independent and combined effects exerted on the production of cytokines IL-1, IL-6, TNF-α, TGF-β, and IL-10 and reactive oxygen and nitrogen species (RONS) by leukocytes in women of a reproductive age and postmenopausal women. Methods: ELISA and chemiluminescence methods were used for this purpose. Results: PTS reduced IL-6 and RONS production by 50% and increased IL-10 production 2-fold in postmenopausal women, and it reduced IL-6 production by 80% and RONS production by 50% in women of reproductive age. When PTS and steroid hormonal drugs are used together, there is a general suppression of cytokine and oxidant activity. Conclusions: PTS reduces the production of inflammatory factors by leukocytes and stimulates the production of anti-inflammatory factors, more so in postmenopausal women. Progestins showed greater suppression of pro-inflammatory cytokine and RONS formation and stimulation of anti-inflammatory cytokines for women of reproductive age and dexamethasone showed such results for postmenopausal women. Full article

Background: Erectile dysfunction (ED) is a disease whose occurrence is steadily increasing worldwide. This pathology is multifactorial and often combined with other diseases. ED of organic genesis in 50–80% of men is vasculogenic. Methods: A survey was conducted of 88 men (aged 44 to 62) who complained of erectile dysfunction. It consisted of a questionnaire administered according to the protocols “International Index of Erectile Function” and “Aging Male Screening”, and was followed by a color Doppler ultrasound (Logiq 9 ExpertGE with a 7 MHz linear transducer using B mode) and penile scintigraphy (single-photon emission computed tomography). The procedures were initially performed at rest, then during pharmacologically induced erection, which was achieved through the intake of phosphodiesterase-5 (PDE5) inhibitors. Patients who did not respond to pharmacological stimulation and had IIEF scores below 5–7 were offered surgical treatment—penile prosthesis followed by histological examination of the tissue of the corpus cavernosum. Statistical analysis was carried out using Microsoft Excel and STATISTICA 10.0 software. The Mann–Whitney U test was used to assess differences between quantitative variables, with the significance level set at p ≤ 0.05. Results: Penile scintigraphy shows high sensitivity (85.2%) and specificity (83.3%), outperforming color Doppler ultrasonography in detecting vasculogenic ED. Conclusion: Penile scintigraphy is demonstrated to be a highly informative method, allowing us to analyze the condition of the magistral and organ blood flow, as well as the microcirculatory bed of the cavernous bodies of the penis. This improves the effectiveness of this method in diagnosing various types of vasculogenic erectile dysfunction (ED), which opens opportunities for its use together with ultrasound examination when the latter is less informative. Full article

Background: Enterobiasis, caused by Enterobius vermicularis, is recognized as a common intestinal helminthiasis worldwide. Despite multiple surveys in Thailand, no pooled synthesis at the country level has been carried out to evaluate prevalence patterns, temporal trends, or vulnerable groups. Therefore, this systematic review and meta-analysis were undertaken to provide an updated and comprehensive estimate of the prevalence of E. vermicularis in Thailand and to identify high-risk populations for targeted interventions. Methods: The systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO: CRD420251053217). Studies reporting E. vermicularis infection in Thailand were systematically searched in international and Thai databases. Pooled prevalence and odds ratios (ORs) were calculated using random-effects models. Subgroup analyses and meta-regression were performed according to year, region, age, population type, and diagnostic method. Results: A total of 56 studies, including 52,765 participants, were analyzed. The overall pooled prevalence was estimated at 3.6% (95% confidence interval [CI]: 2.1–5.9%), with a decline observed in the subgroup analysis by publication year, from 4.75% in 2000–2009 to 1.15% in 2020–2023. The highest prevalence was reported in Central Thailand (7.93%). High infection rates were found among immigrant children (25.2%), hilltribe children (19.9%), Karen students (15.5%), and children in orphanages (11.4%). A markedly higher prevalence was detected by the Scotch tape method compared with direct smear/concentration (12.9% vs. 0.33%). No significant difference in infection risk was observed between males and females (OR = 1.03, p = 0.65). Conclusions: The pooled prevalence of E. vermicularis in Thailand was estimated at 3.6%, but this figure should be interpreted with caution due to high heterogeneity across studies. More meaningful insights were identified in subgroup analyses, which revealed a temporal decline in prevalence, geographic clustering in Central Thailand, and disproportionately high infection rates among socioeconomically disadvantaged child populations. No statistically significant association was found between gender and risk of infection. These patterns underscore the need for targeted screening, deworming, and hygiene interventions, along with the standardized use of the Scotch tape technique for accurate surveillance and comparability of future studies. Full article

Background: Tetranectin (CLEC3B), a plasminogen-binding protein involved in fibrinolysis and tissue remodeling, has been increasingly studied as a potential diagnostic and prognostic biomarker in cardiovascular disease (CVD). This review synthesizes current evidence on its clinical utility across heart failure (HF), coronary artery disease (CAD), and related conditions. Objectives: To systematically evaluate and synthesize published clinical evidence on the diagnostic and prognostic value of tetranectin in cardiovascular diseases. Methods: A systematic search of PubMed, Google Scholar, and Scopus (January 2010–June 2025) identified original human studies examining associations between tetranectin (CLEC3B) and cardiovascular diseases, including heart failure, coronary artery disease, myocardial infarction, and cardiometabolic conditions. Eligible studies included adult cohorts with observational designs; experimental, in vitro, and pediatric studies were excluded. Two reviewers independently extracted data on study design, population characteristics, biomarker assessment, and outcomes, resolving discrepancies by consensus. Results: Twelve studies were included. Tetranectin levels were consistently lower in patients with CAD, MI, and advanced HF compared to controls. Higher circulating TN levels were associated with reduced risk of HF onset, cardiovascular death, and hospitalization. In two studies, combining tetranectin with NT-proBNP improved diagnostic accuracy over NT-proBNP alone. Mechanistic studies revealed correlations between TN expression and fibrosis-related gene pathways, supporting its biological relevance. Conclusions: Tetranectin shows consistent promise as a diagnostic and prognostic biomarker in cardiovascular disease, particularly in heart failure and coronary artery disease. Its involvement in fibrotic remodeling, plasminogen activation, and vascular homeostasis underlines biological pathways relevance. Combining tetranectin with established biomarkers may improve cardiovascular risk stratification and guide more personalized therapeutic strategies. Further large-scale and longitudinal studies are needed to validate its clinical utility across diverse settings. Full article

Background: Heart rate (HR) and HR variability (HRV) are valid indices of psychophysical stress. Healthy individuals typically exhibit high vagal tone, as indicated by vagally mediated HRV (vmHRV) values. Despite current knowledge, HRV differences between anxious subjects and controls during a cognitive task have not yet been studied. Methods: Anxious people were compared to controls through the State–Trait Anxiety Inventory (STAI-Y), both considering State Anxiety (S-Anxiety) and Trait Anxiety (T-Anxiety) one at a time. Subsequently, a psychophysiological stress profile (PSP) was conducted to record HRV values (i.e., SDNN, RMSSD, and HF) at baseline and under induced stress with an electrocardiogram (ECG). During the stress test, the digit span forward task was conducted. Results: Significant differences were described by dividing the sample by S-Anxiety in the baseline values of log-HF (t = 2.68; p = 0.05; d = 0.85) and log-RMSSD (t = 2.34; p = 0.01; d = 0.74). Dividing the sample by T-Anxiety, significant differences were found in the reactivity (t = −2.26; p = 0.03; d = −0.70) and recovery (t = 2.11; p = 0.04; d = 0.66) log-HF values. Additionally, reactivity log-HF and recovery log-RMSSD values demonstrated significant discriminative power of 68% and 68%, respectively, in accurately identifying individuals with anxiety, as measured by T-Anxiety. Lastly, an association was found between the baseline HR value and the equivalent point of digit span forward in both the anxious (r = 0.59, p = 0.01) and control (r = −0.45, p = 0.05) groups. Conclusions: Although a high vmHRV is considered a protective factor against stress, our findings found that a reduced HRV modulation can distinguish a group of people with significant symptoms of anxiety and hinder cognitive efficiency. Full article

Left ventricular diastolic dysfunction (LVDD) is characterized by impaired ventricular relaxation and increased chamber stiffness during diastole, resulting in increased left ventricular filling pressures. It represents a highly prevalent yet frequently underdiagnosed cardiac condition with significant clinical implications, serving as a major contributor to heart failure with preserved ejection fraction (HFpEF), particularly among elderly individuals and those with hypertension, diabetes mellitus, obesity, or coronary artery disease. Multiple studies have identified the progression of LVDD as a marker of adverse prognosis, associated with increased morbidity and mortality, highlighting the importance of early recognition and targeted therapeutic strategies to improve diastolic function and clinical outcomes. This review summarizes the pathophysiology, current diagnostic strategies, and treatment options for LVDD, emphasizing its importance in clinical practice. Full article

Background: Juvenile fibromyalgia (JFM) is a chronic pain disorder characterised by widespread musculoskeletal pain, functional impairment, fatigue, and mood disturbances. Treatment remains challenging, considering the multifactorial nature of the condition and the limited high-quality evidence supporting pharmacological or non-pharmacological interventions. Objectives: This review aimed to critically appraise level I evidence from randomised controlled trials assessing the efficacy and safety of pharmacological and non-pharmacological treatments for adolescents with JFM. Methods: Seven published peer-reviewed clinical trials were examined, including studies investigating duloxetine, milnacipran, pregabalin, cognitive-behavioural therapy (CBT), and the integrated Fibromyalgia Integrative Training Teens (FIT) program, which combines CBT with neuromuscular training. Outcomes of interest included pain intensity, functional disability, depression symptoms, physical activity, and adverse events. Results: Pharmacological agents such as duloxetine, milnacipran, and pregabalin demonstrated modest improvements in pain, but failed to produce consistent benefits in function or mood, and were associated with a high incidence of adverse effects. CBT significantly improved functional disability and depression symptoms, yet it had a limited impact on pain reduction or objectively measured activity levels. The FIT Teens program showed superior outcomes in pain intensity and biomechanical function compared to CBT alone, suggesting a synergistic effect of combining psychological and physical reconditioning strategies. Conclusions: Current evidence supports the use of multimodal treatment approaches in JFM. Non-pharmacological interventions, particularly when integrated with structured exercise, offer meaningful benefits with minimal safety concerns. Larger, methodologically rigorous trials are needed to establish optimal treatment pathways and long-term outcomes for this complex and underserved paediatric population. Full article

Background/Objectives: This study aimed to profile the molecular variants of muscle-invasive bladder cancer (MIBC) based on immunohistochemical analysis and to make a correlation with morphological characteristics in a series of 100 consecutive patients. Methods: A retrospective single-center study was conducted on 100 consecutive cases of MIBC (2021–2024). A selected immunohistochemical (IHC) panel (including CK5/6, CK20, and p16) was applied in all cases to classify the tumors into known molecular variants (luminal papillary, luminal non-specified, luminal unstable, stroma-rich, basal/squamous, neuroendocrine-like). Results: Seven molecular subtypes are identified: basal (33%), luminal papillary (24%), luminal unstable (16%), luminal non-specified (10%), basoluminal (double-positive) (9%), neuroendocrine-like (double-negative with neuroendocrine morphology) (6%), and stroma-rich (2%). This distribution largely matches published data (Consensus Classification and The Cancer Genome Atlas (TCGA)), with minor differences (e.g., a lower share of the stroma-rich variant). A strong correlation is found between the histological subtypes of some tumors and their molecular variant (χ², p < 0.001): for example, all cases of urothelial carcinoma with squamous differentiation are basal, micropapillary tumors are entirely luminal, and small-cell carcinomas are neuroendocrine-like. Conclusions: The results demonstrate that the morphological subtype of urothelial carcinoma largely predetermines the molecular profile. Combining classic histopathology with IHC-based profiling allows for a more complete characterization of the tumor and aids prognosis and personalized treatment in MIBC. Full article

Background: Huntington’s disease (HD) causes progressive motor dysfunction, with chorea as its hallmark symptom. Vesicular monoamine transporter 2 (VMAT 2) inhibitors (tetrabenazine, deutetrabenazine, valbenazine) are established symptomatic therapies, while dopamine stabilizers (pridopidine, ordopidine) are emerging therapies, but their net benefit and safety remain uncertain. Methods: Seven databases were searched through May 2025 following PRISMA guidelines. Random effects meta-analyses calculated mean differences (MDs) for the Unified Huntington Disease Rating Scale total motor score (UHDRS TMS) and total maximal chorea score (TMC), plus risk ratios (RRs) for adverse events (AEs). Trial Sequential Analysis (TSA) applied a Lan DeMets O’Brien Fleming α spending function with 80% power. Results: Seven randomized trials (1431 participants) met inclusion criteria. VMAT 2 inhibitors significantly improved motor outcomes versus placebo (UHDRS TMS: MD −3.80, 95% CI −5.76 to −1.83; TMC: MD −3.05, 95% CI −3.84 to −2.26; both I² = 0%). Dopamine stabilizers produced no meaningful change (UHDRS TMS: MD −0.98, 95% CI −2.48 to 0.51; I² = 32%). Neither class increased total AEs (VMAT 2: RR 1.21, 95% CI 0.99 to 1.48; dopamine stabilizers: RR 1.05, 95% CI 0.92 to 1.20; both I² = 0%). TSA confirmed robust evidence for VMAT 2 benefits on TMC but indicated additional data are required to verify dopamine stabilizer effects on UHDRS TMS. Trial sequential analysis confirmed the reliability of VMAT2 for TMC; however, the sample size was insufficient to draw conclusions about the effects of dopamine stabilizers on UHDRS TMS or their safety outcomes, indicating that additional data are needed. Conclusions: VMAT-2 inhibitors may suggest potential improvements in motor symptoms in Huntington’s disease, while current evidence does not demonstrate a significant benefit of dopamine stabilizers. The safety profiles of both treatments appear generally comparable to placebo. Further rigorous and long-term studies are required to better establish their efficacy and safety. Full article

Background: Brain metastases (BMs) are a common and challenging complication of non-small cell lung cancer (NSCLC), historically associated with a poor prognosis. The development of targeted therapies, specifically tyrosine kinase inhibitors (TKIs) for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene alterations, has significantly improved treatment outcomes. Methods: This article reports and evaluates the efficacy of different generations of TKIs for NSCLC with BMs. The primary endpoints assessed are intracranial objective response rates (IC-ORR), progression-free survival (PFS), and overall survival (OS). The analysis considers TKIs as monotherapy and in combination with radiotherapy. It also examines the impact of newer generation TKIs with enhanced blood–brain barrier (BBB) penetration on intracranial control. The report further discusses the integration of systemic therapy with local modalities like stereotactic radiosurgery (SRS) and the safety profiles of these agents, including central nervous system (CNS) and metabolic adverse events. Results: Newer generation TKIs demonstrate significantly enhanced BBB penetration, resulting in superior intracranial control compared to older generations. These agents show remarkable intracranial activity, contributing to improved IC-ORR, PFS, and OS. The optimal integration of systemic therapy with local modalities, such as SRS, is still under investigation. Treatment with these TKIs is associated with distinct safety profiles, including novel CNS and metabolic adverse events, which require careful management due to prolonged treatment durations. Conclusions: The management of CNS metastases in NSCLC is evolving towards more proactive and personalized therapeutic strategies. Newer generation TKIs have profoundly reshaped the treatment landscape by offering superior intracranial control. Further research is needed to determine the optimal integration of these systemic therapies with local modalities and to effectively manage the associated adverse events. Full article

Background: “Long COVID” refers to a condition in which individuals continue to experience persistent signs and symptoms even after recovering from the initial COVID-19 infection. Signs and symptoms that persist can affect multiple organs in the body. Vitamin D is an essential nutrient that plays a crucial role, particularly in the immune system, and may be linked to the development of long COVID. Objective: The study aimed to investigate the association between vitamin D levels and the prevalence of long COVID signs and symptoms in COVID-19 patients. Materials and Methods: The study enrolled 170 COVID-19 patients with mild signs and symptoms and confirmed COVID-Ag or RT-PCR tests. The subjects were aged 18–59 years. All patients had 25(OH)D levels measured within 60 days of COVID-19 diagnosis and had been followed for at least 3 months post-infection. Data collected included demographic characteristics, serum 25(OH)D levels, and self-reported long COVID signs and symptoms questionnaire responses. Results: The study results indicated a female-to-male ratio of 1.1:1 and a mean age of 45.87 ± 8.65 years; of these, 62.4% received three doses of the COVID-19 vaccine, and 64.7% developed long COVID. The most prevalent signs and symptoms were respiratory (55.3%), skin (50.6%), and general (39.4%). The median blood vitamin D level was 22.96 ng/mL, with 41.2% of subjects having insufficient levels, 30.6% having deficient levels, and 28.2% having sufficient levels. Patients with long COVID had significantly lower vitamin D levels compared with those without long COVID (21.52 ng/mL vs. 25.46 ng/mL; p < 0.05). Multivariable analysis found that vitamin D deficiency was significantly associated with overall long COVID signs and symptoms (Adj. OR, 5.80 [95% CI: 2.10, 16.13]). Additionally, vitamin D deficiency significantly increased the number of long COVID systemic signs and symptoms (Adj. IRR, 3.30 [2.12, 5.12]). Conclusion: Assessing and maintaining vitamin D levels, vitamin D supplementation, and sunlight exposure in COVID-19 patients can reduce the risk and severity of long-term COVID-19 signs and symptoms. Full article

Background: Allergic diseases in early childhood are influenced by genetic predisposition and modifiable early-life exposures, including epigenetic mechanisms. Understanding the interplay between environmental factors and allergy development in children with atopic heredity is critical for prevention strategies. Objective: To investigate the associations between selected early-life environmental exposures and the development of allergic conditions in children with a positive family history of atopy. Methods: A cross-sectional study was conducted among 120 children aged 2 years (±5 months) with atopic heredity, recruited at the Medical University of Varna, Bulgaria (2017–2020). Data on sociodemographic background, prenatal exposures, birth mode, feeding practices, pet contact, daycare attendance, and infectious burden were collected via structured questionnaires and medical records. Allergic outcomes (food allergy and atopic dermatitis) were physician-confirmed. Statistical analyses included t-tests and chi-square tests. Results: Food allergy was diagnosed in 23.3% and atopic dermatitis in 21.7% of participants. Formula feeding was significantly more common in children with food allergy (66.7% vs. 38.1%; p = 0.020). A lower maternal pregnancy experience score was significantly associated with both food allergy (p = 0.021) and overall allergic outcomes (p = 0.004). Indoor smoking was more common in households of non-allergic children (p = 0.034). Children with food allergy had significantly more rhinopharyngitis episodes (p = 0.014) and longer infection duration. Higher gastroenteritis frequency and hospitalization rates were also noted in food-allergic children. Conclusions: In children with atopic heredity, early formula feeding, prenatal maternal stress, and infection burden were associated with increased risk of allergic conditions. This study underscores the importance of early-life psychosocial and environmental influences, possibly mediated by epigenetic mechanisms, in the development of childhood allergies. These findings highlight novel targets for early prevention and warrant further longitudinal research. Full article

Purpose: The aim of this paper is to study the visual outcomes, changes in higher order aberration (HOA) and corneal densitometry after debridement and excimer laser phototherapeutic keratectomy (PTK) for the treatment of Salzmann nodular degeneration (SND). Methods: This monocentric study includes 69 eyes from 54 patients who underwent debridement and PTK for SND (mean follow-up time of 447.1 ± 597.7 days post-operatively). The following parameters were measured before and after PTK: best corrected visual acuity (BCVA) in logMAR, sphere, cylinder, calculated spherical equivalent (SPHQ), mean and maximum refractive power, astigmatism, HOA, corneal density and thickness. Patients were divided into two cohorts depending on additional visual acuity limitations (VAL). Results: Mean visual acuity improvement was 0.16 ± 0.21 logMAR (p < 0.001), independent of additional VAL, and was associated with normalization of the cornea (hyperopic reduction by 2.13 ± 2.60 dpt, p < 0.001), reductions in cylinder (1.49 ± 2.44 dpt, p < 0.001) and corneal astigmatism (3.01 ± 3.39 dpt, p < 0.001). HOA was reduced by 0.77 ± 1.11 µm (p < 0.001) and corneal density by 6.08 ± 16.45 gray scale units (GSUs) in the center (p = 0.019) and by 9.32 ± 12.08 GSUs in the mid-periphery (p < 0.001). Haze occurred in 26.1% of patients (15.9% mild; 10.1% moderate). Re-PTK was necessary in 5.8%. Conclusions: PTK is a low-complication method for visual improvement in patients with SND, regardless of additional VAL, and is associated with a normalization of corneal parameters. HOA, corneal density and K_max were reduced significantly and showed a correlation with visual acuity, implying that these objective parameters may have a good predictive value for visual acuity. Full article

Background: Emotional eating (EmE) is a maladaptive eating behavior that has been frequently observed among university students, possibly due to academic stress and lifestyle changes. However, its specific assessment in health science students has been poorly addressed, even though this population faces high levels of academic stress and emotional burden. Objective: This study explores the association between self-perceived health status, life satisfaction, and EmE among university students in the health field on the north coast of Peru. Methods: A cross-sectional study was conducted on a sample of 1213 students. Self-perceived health, life satisfaction, and EmE were assessed using validated instruments. In addition, sociodemographic data were considered as covariates and possible confounding factors. T-tests, chi-square tests, and Poisson regression with robust variance were applied. Results: EmE was more prevalent in women (78.0%) than in men (66.8%; p < 0.001). In addition, an inverse association was observed between self-perceived health and emotional eating: students with average self-perceived health (adjusted OR = 0.88; 95% CI: 0.83–0.94) and those with high self-perceived health (adjusted OR = 0.75; 95% CI: 0.69–0.81) showed a progressively lower prevalence of EmE compared to those with low self-perceived health. Similarly, high life satisfaction was associated with a lower prevalence of EmE (adjusted PR = 0.88; 95% CI: 0.80–0.96). Conclusions: Low self-perceived health and life dissatisfaction were significantly associated with a higher probability of EmE in medical and nursing students. These results highlight the need to strengthen university programs on mental health, emotional regulation, and subjective well-being promotion as strategies to prevent maladaptive eating behaviors in academic settings, considering gender. Full article

Background: Phosphaturic mesenchymal tumours secreting fibroblast growth factor 23 (hereinafter referred to as FGF23+ PMT) are rare neoplasms that can cause hypophosphataemic osteomalacia, owing to excessive FGF23 production. Mast cells (MCs) play a key role in tumour biology by modulating proliferative activity of atypical cells, resistance to innate and acquired immunity, angiogenesis, and metastatic behaviour. However, MCs associated with FGF23+ PMT have not previously been investigated. This study, to our knowledge, is the first to characterise features of the tumour microenvironment through spatial phenotyping of the immune and stromal landscape, together with histotopographic mapping of intercellular MC interactions with other subcellular populations in FGF23+ PMT. Methods: Histochemical staining (haematoxylin and eosin, toluidine blue, Giemsa solution, picro-Mallory protocol, silver impregnation), as well as monoplex and multiplex immunohistochemical staining with spatial phenotyping, were performed to detect atypical FGF23-secreting cells, immune cells (CD3, CD4, CD8, CD14, CD20, CD38, CD68, or CD163), stromal components (CD31, α-SMA, or vimentin), and specific MC proteases (tryptase, chymase, or carboxypeptidase A3). Bioinformatics analysis using artificial intelligence technologies was applied for spatial profiling of MC interactions with tumour, immunocompetent, and stromal cells in the tumour microenvironment. Results: Bioinformatic analysis of the entire tumour histological section, comprising over 70,000 cells stained using monoplex and multiplex immunohistochemical protocols, enabled identification of more than half of the cell population. The most abundant were CD14+ (30.7%), CD163+ (23.2%), and CD31+ (17.9%) cells. Tumour-associated MCs accounted for 0.7% of the total pool of immunopositive cells and included both mucosal and connective tissue subpopulations, predominantly of the tryptase + chymase-CPA3-specific protease phenotype. This pattern reflected combined multidirectional morphogenetic processes in the patient’s FGF23+ PMT. More than 50% of MCs were colocalized with neighbouring cells of the tumour microenvironment within 20 μm, most frequently with monocytes (CD14+CD68+), M2 macrophages (CD68+CD163+), and endothelial cells (CD31+). In contrast, colocalization with atypical FGF23-secreting cells was rare, indicating minimal direct effects on tumour cell activity. Interaction with T lymphocytes, including CD8+, was also infrequent, excluding their activation and the development of antitumour effects. Mapping of MC histotopography validated the hypothesis of their inductive role in monocyte differentiation into M2 macrophages and probable polarisation of macrophages from M1 into M2, thereby contributing to slow tumour growth. MCs were further involved in extracellular matrix remodelling and participated in the formation of pro-osteogenic niches within the FGF23+ PMT microenvironment, leading to pathological osteoid development. Conclusions: This study demonstrated active MC participation in the evolution of the FGF23+ PMT microenvironment. The findings may be applied in translational medicine to develop novel algorithms for personalised therapy in patients with FGF23-secreting tumours, offering an alternative when surgical removal of the tumour is not feasible. Full article

Background: RNF114 gene encodes an E3 ubiquitin ligase involved in immune signaling and regulation of inflammation. Genetic variants, particularly nonsynonymous single-nucleotide polymorphisms (nsSNPs), may interfere with protein function and cause immune diseases such as psoriasis. Although significant, the structural and functional impact of RNF114 nsSNPs is not well understood. Methods: We used comprehensive bioinformatics analyses to predict the functional impact of RNF114 nsSNPs. Deleterious variants were predicted by SIFT, PolyPhen-2, PROVEAN, META-SNP, ESNP&GO, PANTHER, and Alpha-Missense. Protein stability was examined by I-Mutant2.0, and MUpro further contextualized variant effects. Structural modeling was performed by AlphaFold and visualized using UCSF ChimeraX 1.10.1. Additionally, we studied the Conservation using ConSurf and protein-protein interaction by STRING tools. Results: Among 252 available nsSNPs, three mutations—C49R (rs1600868749), R68C (rs745318334), and R68H (rs758000156)—were predicted to have a deleterious and destabilizing effects on the protein structure by all the tools. All three variants were located in extremely conserved residues and were predicted to significantly destabilize the protein structure. Structural modeling demonstrated disruptions in the RNF114 domain structure. STRING analysis revealed interactions of RNF114 with key immune regulators, and pathway enrichment pointed to roles in NF-κB signaling, ubiquitin-mediated proteolysis, and autoimmune disease pathways. Conclusions: In the current study, we predicted three novel, potentially pathogenic RNF114 variants with protein-destabilizing effect that could lead to immune dysregulation. Full article

Background and Objectives: Vitamin D deficiency affects bone health and immune function, especially in children. While universal screening is not cost-effective, targeted screening and supplementation strategies have proven effective. This study evaluates the effectiveness of Romania’s National Vitamin D Screening Programme in detecting vitamin D deficiency in paediatric patients, while also accounting for the impact of the COVID-19 pandemic. Materials and Methods: This retrospective observational study assessed the effectiveness of Romania’s National Vitamin D Screening Initiative in detecting vitamin D deficiency among children admitted to the Clinical Emergency Hospital for Children “Louis Țurcanu”, Timișoara, from January 2018 to December 2024. Serum 25-hydroxyvitamin D levels were analysed in 3596 tested patients out of 22,353 total admitted patients, to evaluate trends from before, during, and after the COVID-19 pandemic. Patients aged 0–18 with at least one admission were included, regardless of diagnosis. Patients in ICU, surgical departments, non-Romanian citizens, and those with life-threatening conditions were excluded. Logistic regression analysis was used to assess programme impact and risk factors for vitamin D insufficiency. Results: The study population had a mean age of 5.36 years, with 53.57% male patients. Patient admissions dropped significantly during pandemic years (mean of 2057 annually in 2020–2022 vs. 4045.5 in pre-/post-pandemic years). Vitamin D insufficiency (<20 ng/mL) peaked at 33.3% in 2020 and 32.5% in 2023, with lowest rates in 2019 (17.2%) and 2021 (16.5%). The National Screening Programme implementation resulted in 57.1% higher odds of vitamin D testing in 2023–2024 compared with 2018–2019 (adjusted OR = 1.571, 95% CI: 1.429–1.726, p < 0.001), with testing rates increasing from 12.6% to 17.5%. Age emerged as the strongest predictor of vitamin D insufficiency, with each additional year associated with 8–9% increased odds of deficiency. Conclusions: The National Vitamin D Screening Programme significantly enhanced detection of vitamin D insufficiency in paediatric populations, despite pandemic-related disruptions. An optimal testing rate of approximately 17% was identified for balancing detection efficiency with resource utilisation. These findings underscore the need for sustained risk-based screening programmes and public health education initiatives to address vitamin D insufficiency in children, particularly in developing countries with limited healthcare resources. Full article

Background: In exercise testing, the ventilatory threshold 1 (VT1) and ventilatory threshold 2 (VT2) are used in lifestyle-related diseases, cardiac rehabilitation, and athletic training. We investigated a VT2 measuring method using a pulse oximeter. Methods: Thirty-four adults (men: 15; women: 19) performed a bicycle ergometer Ramp Test. VT1 values were determined using expiratory gas data. The bifurcation of the curve obtained by designating the pulse rate (PR) as an independent variable and SpO₂/PR as a dependent variable was calculated using the residual sum of squares and defined as the SpO₂ threshold (ST) (SpO₂-Slope method). A second bifurcation with ST as the origin was further defined (ST2). ST2 validity was assessed by comparing and analyzing the differences and correlations with each VT2 obtained by expiratory gas analysis. Results: The correlation between ST2 determined by the SpO₂-Slope method using PR as an index and VT2 obtained from respiratory gas analysis was significant, showing a positive correlation (r = 0.74~0.92; p < 0.01), with most data points falling within the 1.96 ± SD in the Bland–Altman analysis. Conclusions: ST2 values derived from SpO₂ and pulse rate measurements by pulse oximeter may be a valuable VT2 measuring method. Full article

Background: Cognitive and neuropsychological effects of cancer and its treatments have gained increasing attention over the past decade, with growing evidence of persistent deficits across multiple cancer types. While numerous studies have examined these effects, the literature remains fragmented, and no comprehensive bibliometric synthesis has been conducted to map the field’s intellectual structure and emerging trends. Methods: A bibliometric and science mapping analysis was performed using the Scopus database to identify peer-reviewed articles published between 2015 and 2025 on neuropsychological or cognitive outcomes in adult cancer populations. Data from 179 eligible publications were analyzed with VOSviewer and Microsoft Power BI, applying performance metrics and network mapping techniques, including co-authorship, bibliographic coupling, co-citation, and keyword co-occurrence analyses. Results: Publication output increased steadily over the decade, with leading contributions from the Journal of Neuro-Oncology, Psycho-Oncology, and Brain Imaging and Behavior. Co-citation analysis identified three core intellectual pillars: (i) clinical characterization of cancer-related cognitive impairment, (ii) mechanistic and neuroimaging-based investigations, and (iii) neurosurgical and neuropathological research in brain tumors. Keyword mapping revealed emerging themes in sleep and circadian rhythm research, biological contributors to cognitive decline, and scalable rehabilitation strategies such as web-based cognitive training. Collaborative networks, while showing dense local clusters, remained moderately fragmented across disciplines. Conclusions: This review provides the first quantitative, decade-spanning map of cognitive oncology research, highlighting both consolidated knowledge areas and underexplored domains. Future efforts should prioritize methodological standardization, cross-disciplinary collaboration, and integration of cognitive endpoints into survivorship care, with the ultimate aim of improving functional outcomes and quality of life for cancer survivors. Full article