Search Results (2,107)

Background/Objectives: Benign paroxysmal positional vertigo (BPPV) is the most prevalent vestibular disorder encountered in clinical settings and is highly responsive to evidence-based diagnostic and therapeutic interventions. However, variations in practice patterns among physician specialties can compromise timely diagnosis and effective treatment. Understanding these variations is essential for improving clinical outcomes and standardizing care. This study aimed to assess the diagnostic and treatment practices for BPPV among Ear, Nose, and Throat (ENT) specialists, neurologists, general practitioners, and family physicians in Saudi Arabia and to examine how these practices are influenced by clinical experience and patient case exposure. Methods: A cross-sectional, questionnaire-based study was conducted between April 2023 and March 2024 at King Khalid University, Abha, Saudi Arabia. A total of 413 physicians were recruited using purposive sampling. Data were analyzed using IBM SPSS version 24.0. Parametric tests, including one-way ANOVA and chi-square tests, were used to assess differences across groups. A p-value of <0.05 was considered statistically significant. Results: Overall, all physician groups exhibited limited adherence to guideline-recommended positional diagnostic and therapeutic maneuvers. However, ENT specialists and neurologists demonstrated relatively higher compliance, particularly in performing the Dix–Hallpike test, with 46.97% and 26.79% reporting “always” using the maneuver, respectively (p < 0.001, Cramér’s V = 0.22). Neurologists were the most consistent in conducting oculomotor examinations, with 73.68% reporting routine performance (p < 0.001, Cramér’s V = 0.35). Epley maneuver usage was highest among neurologists (86.36%) and ENT specialists (77.14%) compared to family physicians (50.60%) and GPs (67.50%) (p = 0.044). Physicians with 11–15 years of experience and >50 BPPV case exposures consistently showed a greater use of diagnostic maneuvers, repositioning techniques, and guideline-concordant medication use (betahistine 76.67%; p < 0.001). Continuing medical education (CME) participation and the avoidance of unnecessary imaging were also highest in this group (46.67% and 3.33%, respectively; p < 0.001). Conclusions: Significant inter-specialty differences exist in the management of BPPV in Saudi Arabia. Greater clinical experience and higher case exposure are associated with improved adherence to evidence-based practices. Targeted educational interventions are needed, particularly in primary care, to enhance guideline implementation. Full article

Background: Despite the growing demand for amyloid PET quantification, practical challenges remain. As automated software platforms are increasingly adopted to address these limitations, we evaluated the reliability of commercial tools for Centiloid quantification against the original Centiloid Project method. Methods: This retrospective study included 332 amyloid PET scans (165 [¹⁸F]Florbetaben; 167 [¹⁸F]Flutemetamol) performed for suspected mild cognitive impairments or dementia, paired with T1-weighted MRI within one year. Centiloid values were calculated using three automated software platforms, BTXBrain, MIMneuro, and SCALE PET, and compared with the original Centiloid method. The agreement was assessed using Pearson’s correlation coefficient, the intraclass correlation coefficient (ICC), a Passing–Bablok regression, and Bland–Altman plots. The concordance with the visual interpretation was evaluated using receiver operating characteristic (ROC) curves. Results: BTXBrain (R = 0.993; ICC = 0.986) and SCALE PET (R = 0.992; ICC = 0.991) demonstrated an excellent correlation with the reference, while MIMneuro showed a slightly lower agreement (R = 0.974; ICC = 0.966). BTXBrain exhibited a proportional underestimation (slope = 0.872 [0.860–0.885]), MIMneuro showed a significant overestimation (slope = 1.053 [1.026–1.081]), and SCALE PET demonstrated a minimal bias (slope = 1.014 [0.999–1.029]). The bias pattern was particularly noted for FMM. All platforms maintained their trends for correlations and biases when focusing on subthreshold-to-low-positive ranges (0–50 Centiloid units). However, all platforms showed an excellent agreement with the visual interpretation (areas under ROC curves > 0.996 for all). Conclusions: Three automated platforms demonstrated an acceptable reliability for Centiloid quantification, although software-specific biases were observed. These differences did not impair their feasibility in aiding the image interpretation, as supported by the concordance with visual readings. Nevertheless, users should recognize the platform-specific characteristics when applying diagnostic thresholds or interpreting longitudinal changes. Full article

Diclofenac, an aryl-acetic acid derivative from the non-steroidal anti-inflammatory drug class, is the subject of multiple non-clinical and clinical studies regarding its usefulness in treating some dermatologic pathologies with an inflammatory, auto-immune, or proliferative component. Diclofenac is now approved for the topical treatment of actinic keratoses (AK), pre-malignant entities that have the risk of transformation into skin carcinomas. The hypothesis that diclofenac increases granular layer development in the mice tail model, having an anti-psoriatic effect, was demonstrated in a previous study in which 1% and 2% diclofenac ointment was evaluated. The aim of the present study was to perform experimental research on the topical effect of diclofenac in the mice tail model, by testing 4% and 8% diclofenac ointment, which is presented in the first part of the manuscript. In the second part of the manuscript, we also aimed to conduct a literature review regarding topical diclofenac uses in specific dermatological entities by evaluating the articles published in PubMed and Scopus databases during 2014–2025. The studies regarding the efficacy of topical diclofenac in dermatological diseases such as AK and field cancerization, actinic cheilitis, basal cell carcinoma, Bowen disease, Darier disease, seborrheic keratoses, and porokeratosis, were analyzed. The results of the experimental work showed a significant effect of 4% and 8% diclofenac ointment on orthokeratosis degree when compared to the negative control groups. Diclofenac in the concentration of 4% and 8% significantly increased the orthokeratosis degree compared to the negative control with untreated mice (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test) and to the negative control with vehicle (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test). The mean epidermal thickness was increased for the diclofenac groups, but not significantly when compared to the control groups. The results are concordant with our previous experiment, emphasizing the need for future clinical trials on the use of topical diclofenac in psoriasis. Full article

Understanding the molecular basis of endometrial receptivity is crucial for improving implantation outcomes in assisted reproduction, especially for patients with recurrent implantation failure (RIF). This study investigates the timing relationship between microRNA (miRNA) and messenger RNA (mRNA) profiles in the endometrium using simultaneously the endometrial receptivity array (ERA) and the microRNA receptivity assay (MIRA) in 100 RIF patients undergoing euploid blastocyst transfer. The concordance rate between ERA and MIRA was 72% (Kappa = 0.50), suggesting partial overlap in profiling. Patients were stratified by the timing sequence of miRNA relative to mRNA into Fast, Equal, and Slow groups. Those with delayed miRNA expression (Slow group) had significantly lower pregnancy rates (54.5%) than those with synchronous or leading miRNA expression (81.9% and 94.1%, respectively; p = 0.031). Moreover, the Slow group exhibited higher prior implantation failure counts and altered expression in 15 miRNAs, many involved in aging-related pathways. These findings highlight that asynchronous miRNA–mRNA profiles may reflect impaired receptivity and suggest that miRNA-based staging adds valuable diagnostic insight beyond mRNA profiling alone. Dual assessment of mRNA and miRNA profiles may offer additional diagnostic insight into endometrial receptivity but requires further validation before clinical application. Full article

Porcine reproductive and respiratory syndrome virus remains one of the most economically significant pathogens in swine production, with PRRSV-2 being the dominant variant in the United States. While lineage classification has traditionally relied on ORF5 sequencing, recent studies suggest that this single-gene approach may overlook key evolutionary events such as recombination. In this study, we performed whole-genome sequencing and phylogenetic analysis of seven PRRSV-2 isolates collected in the U.S. between 2006 and 2024. Using reference-guided assembly, lineage assignment, and recombination detection with RDP5 and SIMplot, we identified discordant phylogenetic placements between ORF5 and whole genomes in four of the seven isolates. These discordances were explained by multiple recombination events affecting different genomic regions, particularly ORF2–ORF7. In contrast, three isolates showed phylogenetic concordance and no strong evidence of recombination. Our findings demonstrate that recombination plays a significant role in shaping PRRSV-2 evolution and highlight the limitations of ORF5-based lineage classification. Whole-genome surveillance is therefore essential to accurately track viral diversity, detect recombinant strains, and inform control strategies. This work underscores the need for a broader adoption of full-genome analysis in routine PRRSV surveillance and research. Full article

Background/Objectives: Autism spectrum disorders (ASDs) are neurodevelopmental conditions with early onset of clinical manifestations. ASD etiology is highly heterogeneous, with genetic factors being strong determinants of the behavioral problems and neurodevelopmental deficits. Fragile X syndrome (FXS) (OMIM #300624), caused by the transcriptional silencing of the FMR1 gene, represents the most common monogenic cause of autism. Our study included 226 boys with a diagnosis of ASD, for a systematic screening of genetic and epigenetic defects in the FMR1 gene promoter in a Romanian pediatric cohort. Methods: The methods, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and triplet-primed PCR (TP-PCR)/melt curve analysis (MCA), were chosen for their ability to detect the methylation anomalies (the former) as well as repeat expansions in the FMR1 promoter (the latter). Results: Both methods used in our screening generated concordant results, detecting FMR1 full mutation in 4 out of 226 patients (~1.8%). This yield is similar to data obtained in larger studies. Three out of four boys presented the typical clinical features, in correlation with genetic findings. Conclusions: The combined use of MS-MLPA and TP-PCR/MCA-based assay was, in our experience, useful to fully describe the genetic defects responsible for FXS. A significant variability of clinical presentations was observed in our small group of children with FXS, from mild to severe intellectual disability and from atypical to characteristic dysmorphic features, as well as various behavioral problems. Full article

Objective: Physical joint examination is fundamental in rheumatoid arthritis (RA) assessment. This study evaluated the diagnostic accuracy and agreement between standardized and non-standardized physical joint examinations in RA patients using musculoskeletal ultrasound as the reference standard. Methods: We assessed the joints for tenderness and swelling, calculating sensitivity, specificity, and predictive values. Musculoskeletal ultrasound was used as the reference standard, with adjustment for imperfect reference bias. Agreement between the methods was evaluated using the average kappa coefficient. Results: A total of 1496 joints were evaluated. Without adjustment for imperfect reference bias, standardized examination showed higher sensitivity for detecting pain and swelling than non-standardized examination. Specificity was similar for pain but higher for swelling in standardized examination. After bias adjustment, standardized examination sensitivity improved for pain (93.8% vs. 77.3%; 95% CI: 0.14–0.19) and swelling (91.9% vs. 60.0%; 95% CI: 0.29–0.34). Tenderness specificity remained comparable (standardized examination: 75.4%, non-standardized examination: 76.3%), while the non-standardized examination maintained superior swelling specificity (85.7% vs. 77.1%). Standardized joint examination demonstrated significantly higher concordance than non-standardized assessment in evaluating joint tenderness; standardized assessment yielded significantly greater average kappa coefficients under both false-positive-prioritized (0.44 vs. 0.37; p = 0.01) and false-negative-prioritized scenarios (0.59 vs. 0.45; p < 0.0001). For joint swelling, standardized evaluation showed significantly higher concordance when false negatives were considered more critical (0.59 vs. 0.37; p < 0.0001), whereas differences under false-positive prioritization were not statistically significant. Conclusions: Standardization of the physical joint examination significantly improves diagnostic accuracy and agreement in detecting joint tenderness and swelling in patients with rheumatoid arthritis. Implementing a standardized physical examination protocol may enhance disease activity diagnosis and optimize clinical management of RA. Full article

Background/Objectives: Romania remains a tuberculosis (TB) hotspot in the European Union, yet host-derived factors of poor outcomes are poorly characterised. We quantified circulating pro-inflammatory cytokines and examined their interplay with behavioural risk factors, the nutritional status, and the clinical course in adults hospitalised with pulmonary TB. We analysed 80 adults with microbiologically confirmed pulmonary TB and 40 respiratory symptom controls; four TB patients (5%) died during hospitalisation, all within 10 days of admission. Methods: A retrospective analytical case–control study was conducted at the Constanța regional TB referral centre (October 2020—October 2023). Patients with smear- or culture-confirmed TB were frequency-matched by sex, 10-year age band, and BMI class to culture-negative respiratory controls at a 2:1 ratio. The patients’ serum interferon-γ (IFN-γ), interleukin-1α (IL-1α), interleukin-1β (IL-1β), and tumour-necrosis-factor-α (TNF-α) were quantified within 24 h of admission; the neutrophil/lymphocyte ratio (NLR) was extracted from full blood counts. Independent predictors of in-hospital mortality were identified by multivariable logistic regression; factors associated with the length of stay (LOS) were modelled with quasi-Poisson regression. Results: The median TNF-α (24.1 pg mL⁻¹ vs. 16.2 pg mL⁻¹; p = 0.009) and IL-1β (5.34 pg mL⁻¹ vs. 3.67 pg mL⁻¹; p = 0.008) were significantly higher in the TB cases than in controls. TNF-α was strongly correlated with IL-1β (ρ = 0.80; p < 0.001), while NLR showed weak concordance with multiplex cytokine patterns. Among the patients with TB, four early deaths (5%) exhibited a tripling of TNF-α (71.4 pg mL⁻¹) and a doubling of NLR (7.8) compared with the survivors. Each 10 pg mL⁻¹ rise in TNF-α independently increased the odds of in-hospital death by 1.8-fold (95% CI 1.1–3.0; p = 0.02). The LOS (median 29 days) was unrelated to the smoking, alcohol, or comorbidity load, but varied across BMI strata: underweight, 27 days; normal weight, 30 days; overweight, 23 days (Kruskal–Wallis p = 0.03). In a multivariable analysis, under-nutrition (BMI < 18.5 kg m⁻²) prolonged the LOS by 19% (IRR 1.19; 95% CI 1.05–1.34; p = 0.004) independently of the disease severity. Conclusions: A hyper-TNF-α/IL-1β systemic signature correlates with early mortality in Romanian pulmonary TB, while under-nutrition is the dominant modifiable determinant of prolonged hospitalisation. Admission algorithms that pair rapid TNF-α testing with systematic nutritional assessment could enable targeted host-directed therapy trials and optimise bed utilisation in high-burden settings. Full article

Icariin (ICA) is widely recognized for its health benefits. In this work, we examined the intermolecular interactions between ICA and proteinase K (PK) via multi-spectroscopic techniques and molecular simulations. The experimental findings revealed that ICA quenched the fluorescence emission of PK by forming a noncovalent complex. Both hydrogen bonding and van der Waals interactions are essential for the complex’s formation. Then Förster resonance energy transfer (FRET), competitive experiments, and synchronous fluorescence spectroscopy were adopted to verify the formation of the complex. Molecular docking studies demonstrated that ICA could spontaneously bind to PK by hydrogen bonding and hydrophobic interactions, which is consistent with the spectroscopic results. The PK-ICA complex’s dynamic stability was evaluated using a 50 ns molecular dynamics (MD) simulation. The simulation results revealed no significant structural deformation or positional changes throughout the entire simulation period. The complex appears to be rather stable, as seen by the average root-mean-square deviation (RMSD) fluctuations for the host protein in the PK-ICA complex of 1.08 Å and 3.09 Å. These outcomes of molecular simulations suggest that ICA interacts spontaneously and tightly with PK, consistent with the spectroscopic findings. The approach employed in this research presents a pragmatic and advantageous method for examining protein–ligand interactions, as evidenced by the concordance between empirical and theoretical findings. Full article

Cattle–yak, a hybrid of yak and cattle, exhibits significant heterosis but male infertility, hindering heterosis fixation. Although extensive research has been conducted on transcriptional mechanisms in the testes of cattle–yak, the understanding of their translational landscape remains limited. In this study, we characterized the translational landscape of yak and cattle–yak based on Ribo-seq technology integrated with RNA-seq data. The results revealed that gene expression was not fully concordant between transcriptional and translational levels, whereas cattle–yak testes exhibited a stronger correlation across these two regulatory layers. Notably, genes that were differentially expressed at the translational level only (MEIOB, MEI1, and SMC1B) were mainly involved in meiosis. A total of 4,236 genes with different translation efficiencies (TEs) were identified, and the TEs of most of the genes gradually decreased as the mRNA expression level increased. Further research revealed that genes with higher TE had a shorter coding sequence (CDS) length, lower GC content, and higher normalized minimum free energy in the testes of yaks, but this characteristic was not found in cattle–yaks. We also identified upstream open reading frames (uORFs) in yak and cattle–yak testes, and the sequence characteristics of translated uORFs and untranslated uORFs were markedly different. In addition, we identified several short polypeptides that may play potential roles in spermatogenesis. In summary, our study uncovers distinct translational dysregulations in cattle–yak testes, particularly affecting meiosis, which provides novel insights into the mechanisms of spermatogenesis and male infertility in hybrids. Full article

Background and Objectives: General-purpose multimodal large language models (LLMs) are increasingly used for medical image interpretation despite lacking clinical validation. This study evaluates the diagnostic reliability of ChatGPT-4o and Claude 2 in photographic assessment of adolescent idiopathic scoliosis (AIS) against radiological standards. This study examines two critical questions: whether families can derive reliable preliminary assessments from LLMs through analysis of clinical photographs and whether LLMs exhibit cognitive fidelity in their visuospatial reasoning capabilities for AIS assessment. Materials and Methods: A prospective diagnostic accuracy study (STARD-compliant) analyzed 97 adolescents (74 with AIS and 23 with postural asymmetry). Standardized clinical photographs (nine views/patient) were assessed by two LLMs and two orthopedic residents against reference radiological measurements. Primary outcomes included diagnostic accuracy (sensitivity/specificity), Cobb angle concordance (Lin’s CCC), inter-rater reliability (Cohen’s κ), and measurement agreement (Bland–Altman LoA). Results: The LLMs exhibited hazardous diagnostic inaccuracy: ChatGPT misclassified all non-AIS cases (specificity 0% [95% CI: 0.0–14.8]), while Claude 2 generated 78.3% false positives. Systematic measurement errors exceeded clinical tolerance: ChatGPT overestimated thoracic curves by +10.74° (LoA: −21.45° to +42.92°), exceeding tolerance by >800%. Both LLMs showed inverse biomechanical concordance in thoracolumbar curves (CCC ≤ −0.106). Inter-rater reliability fell below random chance (ChatGPT κ = −0.039). Universal proportional bias (slopes ≈ −1.0) caused severe curve underestimation (e.g., 10–15° error for 50° deformities). Human evaluators demonstrated superior bias control (0.3–2.8° vs. 2.6–10.7°) but suboptimal specificity (21.7–26.1%) and hazardous lumbar concordance (CCC: −0.123). Conclusions: General-purpose LLMs demonstrate clinically unacceptable inaccuracy in photographic AIS assessment, contraindicating clinical deployment. Catastrophic false positives, systematic measurement errors exceeding tolerance by 480–1074%, and inverse diagnostic concordance necessitate urgent regulatory safeguards under frameworks like the EU AI Act. Neither LLMs nor photographic human assessment achieve reliability thresholds for standalone screening, mandating domain-specific algorithm development and integration of 3D modalities. Full article

Background: Infectious complications are common after percutaneous nephrolithotomy (PCNL). Clinical guidelines recommend, previous to surgery, prolonged antibiotic regimens in patients with preoperative positive urine cultures to reduce infectious risk. However, such strategies may increase selective pressure and promote antimicrobial resistance. Evidence supporting the use of a single antibiotic dose tailored to culture sensitivity in these cases is limited but emerging. Methods: We conducted a retrospective observational study including 187 PCNL procedures performed between 2021 and 2023 under an individualized antibiotic prophylaxis protocol. Patients with negative or contaminated urine cultures received a single empirical dose, while those with recent positive cultures received a single dose based on antimicrobial susceptibility testing. Postoperative complications—including fever, sepsis, and a composite outcome—were analyzed through multivariable logistic regression, comparing high- and low-risk patients. Results: A total of 67.9% of procedures were performed in patients meeting at least one high-risk criterion, including a positive preoperative urine culture in 32.1%. The overall incidence of infectious complications was 11.9% (fever 8.7%, sepsis 3.2%), with no significant differences between risk groups. A low concordance was observed between preoperative and intraoperative urine cultures (Spearman = 0.3954). Conclusions: A single preoperative antibiotic dose adjusted to the antibiogram, even in patients with a positive urine culture, was not associated with increased infectious complications. This approach is an initial step that supports a rational and individualized prophylactic strategy aligned with the goals of antimicrobial stewardship programs (ASPs). Full article

Background: Interprofessional collaboration (IPC) is considered fundamental for integrated, high-quality woman-centered care. This study analyzes concordance/differences in the perspectives of midwives and physicians on IPC and Equitable Communication (EC) in prenatal/postpartum (PPC) and birth care (BC). Methods: The short form of the ICS Scale (ICS-R with eight items) adapted for the midwifery context, and the EC scale (three items) were completed by 293 midwives and 215 physicians in Germany. Profession- and the setting-specific differences were analyzed using t-tests and ANOVA with repeated measurements. Confirmatory factor analysis with nested model comparisons test the fairness of the scales. Results: Midwives’ ratings of all IPC aspects were systematically lower than physicians’ in both care settings (variance component professional group: η²_p = 0.227/ 0.318), esp. for EC (d = 1.22–1.41). Both groups rated EC higher in BC. The setting effect was less pronounced among physicians for the ICS-R items than among midwives. Violations of test fairness reveal validity deficiencies when using the aggregated EC sum score for group comparisons. Conclusions: Fundamental professional differences were found in the IPC assessment between physicians and midwives. The results enhance the understanding of IPC dynamics and provide starting points for action to leverage IPC’s potential for woman-centered care. Full article

Microsatellite instability (MSI) is a clinically important biomarker for predicting responses to immune checkpoint inhibitors and identifying individuals with Lynch syndrome. Although MSI detection has been incorporated into Illumina’s next-generation tumor sequencing workflows, interpretation of the results remains challenging due to the absence of standardized thresholds and reporting criteria. In this retrospective study, we assessed the performance of MSI detection using Illumina’s targeted NGS panels—TruSight Tumor 170 and TruSight Oncology 500. The NGS-based MSI results were compared to those obtained by the reference method, MSI-PCR, across multiple tumor types in a real-world cohort of 331 cancer patients. The NGS method demonstrated high concordance overall (AUC = 0.922), though sensitivity was lower in colorectal cancers (AUC = 0.867) due to broader score variability and overlapping distributions. Our findings support the clinical utility of Illumina’s NGS-derived MSI scores for identifying MSI-H tumors, with a recommended MSI score cut-off value of ≥13.8%. Additionally, a borderline group was introduced, defined by an MSI score ranging from ≥8.7% to <13.8%. Within this range, the integration of TMB into the MSI classification workflow significantly improves diagnostic accuracy. For samples that remain inconclusive, orthogonal confirmation using MSI-PCR is advised to ensure accurate MSI classification. Full article

Concerns about mycotoxin contamination by Alternaria spp. in tomato-based products emphasize the need for understanding the effect of the environment on their production. In the current study, we focused on three species frequently associated with tomato (A. alternata, A. solani, and A. tenuissima) by evaluating the effects of different temperatures (5 to 40 °C) and substrata (PDA and V8) on mycelial growth and the production of mycotoxins (alternariol, alternariol monomethyl ether, and tenuazonic acid). Both biological processes were supported between 5 and 35 °C, with optimal temperatures between 20 and 30 °C, depending on the species. Temperature and its interaction with species significantly (p < 0.05) affected both processes. However, the species factor alone was not significant (p > 0.05), indicating that environmental conditions affect Alternaria spp. growth and mycotoxin production more than the species itself does. Mathematical equations were developed to describe the effect of temperature on mycelial growth, as well as on the production of AOH, AME, and TeA, for each Alternaria species. High concordance (CCC ≥ 0.807) between observed and predicted data and low levels of residual error (RMSE ≤ 0.147) indicated the high goodness of fit of the developed equations, which may be used for the development of models to predict Alternaria contamination both in field and during post-harvest storage. Full article