Search Results (5,117)

Rapid detection and differentiation of Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM) are crucial for appropriate treatment selection. The NeoPlex™ TB/NTM Detection Kit is a PCR assay that simultaneously detects MTBC and NTM and identifies five clinically important NTM species (M. intracellulare, M. avium, M. kansasii, M. abscessus subsp. abscessus, and M. abscessus subsp. massiliense). We evaluated its comparative analytical performance using 200 stored nucleic acid extracts from respiratory and non-respiratory MTBC- or NTM-positive clinical specimens after excluding 27 specimens without interpretable species-level results. Results were compared with those of a line probe assay (LPA), which formed the reference test. Concordance with the LPA was 93.0%, including 96.9% for MTBC and 92.3% for NTM. The NeoPlex assay correctly differentiated all MTBC- and NTM-positive specimens included in the study cohort. For species-level identification, sensitivity and specificity were 98.9% and 100% for M. intracellulare, 97.6% and 100% for M. avium, 82.4% and 100% for M. kansasii, 79.0% and 100% for M. abscessus subsp. abscessus, and 100% and 100% for M. abscessus subsp. massiliense, respectively. These findings suggest that this multiplex PCR assay enables rapid, accurate detection and differentiation of MTBC and NTM species directly from clinical samples. Full article

Automatic Drum Transcription (ADT) remains challenging due to overlapping spectral content among drum instruments, dense transient activity, and the increased difficulty associated with fine-grained full-kit transcription. This study investigates whether combining explicit spectral structuring with temporally extended modeling improves ADT performance under a controlled evaluation protocol. A frequency-structured architecture is proposed that integrates a convolutional front end, a Frequency-Structured Soft-Gated Module (FSSM) for coarse frequency-aware processing, and a Dilated Conformer encoder for multi-scale temporal context modeling while preserving frame-level output alignment. Experiments are conducted on the ENST Drums dataset using both 3-class and consolidated 8-class transcription settings. Under a fixed ±50 ms event-level evaluation protocol, the proposed model achieved mean Micro-F1 scores of 0.920 ± 0.001 and 0.872 ± 0.002 in the 3-class and 8-class settings, respectively, outperforming a reproduced CRNN baseline trained and evaluated under identical preprocessing, training, and evaluation protocols. Ablation studies indicate that FSSM contributes the largest performance improvement among the evaluated architectural components, while class-wise analyses show improvements across all instrument categories in the 8-class setting. Zero-shot evaluation on external datasets further demonstrates that the proposed architecture maintains higher performance than the baseline under distribution shift, although substantial degradation remains relative to in-domain evaluation. These findings suggest that combining explicit spectral structuring and temporally extended modeling can improve full-kit drum transcription performance under the evaluated conditions while highlighting the continuing challenges of cross-dataset generalization. Full article

Hepatocellular carcinoma is one of the most aggressive malignancies worldwide, with limited therapeutic options. Boswellia serrata Roxb., an Indian medicinal tree, produces a resin rich in essential oil and boswellic acids, particularly acetyl-11-keto-β-boswellic acid (AKBA), with demonstrated antiproliferative and pro-apoptotic activities. This study investigated the cytotoxic effects of B. serrata essential oil and AKBA on hepatocarcinoma Huh-7 cells in both monolayer and three-dimensional spheroid cultures and characterized the underlying molecular targets. Essential oil was extracted and analyzed by gas chromatography-mass spectrometry (GC-MS). Cytotoxicity was assessed using the cell counting kit-8 (CCK-8). Three-dimensional spheroid cultures were also established to evaluate anti-tumoral potential. Expression of cyclin D1, cyclin-dependent of kinase 4 (CDK4) (cyclin-dependent kinase inhibitor 1A (p21), E-cadherin, (alpha fetoprotein) AFP, epithelial cell adhesion molecule (EpCAM), Myeloid cell leukemia-1 (Mcl-1), and caspase-3 was analyzed by western blot. In addition, an in silico analysis was performed on the main constituents of B. serrata essential oil targeting 5-lipoxygenase (5LO). The results showed cytotoxic effects, with AKBA exhibiting greater potency than the essential oil. Cytotoxicity was associated with caspase-3-mediated apoptosis, with minimal effects on cell cycle and epithelial–mesenchymal transition markers. The in silico analysis predicted that some compounds may act as competitive inhibitors of the 5LO at the catalytic site and partially activate pro-apoptotic pathways. These data support the potential of B. serrata-derived compounds as novel anti-hepatocarcinoma agents, with AKBA and longifolene as leads for further preclinical and clinical research. Full article

Background/Objectives: Serum 25-hydroxyvitamin D [25(OH)D] is a clinically used biomarker of vitamin D nutritional status, although it is also influenced by sunlight exposure, supplementation, season, and other host factors. Short-term functional status after extracorporeal shock wave therapy (ESWT) for lateral epicondylitis varies. We evaluated whether serum 25(OH)D level and status were associated with 12-week functional outcomes among ESWT-treated patients. Methods: This single-center retrospective cohort included 62 adults with lateral epicondylitis who received outpatient ESWT and had baseline and 12-week assessments. Baseline variables included grip strength ratio, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, serum 25(OH)D measured using the Architect 25-OH D vitamin kit, common extensor tendon (CET) thickness, age, sex, and body mass index. Multivariable linear regression was used in an analysis-of-covariance framework. Serum 25(OH)D was assessed continuously and as <20 versus ≥20 ng/mL in exploratory threshold analysis. Results: Serum 25(OH)D was 21.0 ± 8.4 ng/mL; 30 patients (48.4%) had <20 ng/mL, 22 (35.5%) had 20–29.9 ng/mL, and 10 (16.1%) had ≥30 ng/mL. QuickDASH decreased from 42.0 ± 17.4 to 27.0 ± 13.7, and grip strength ratio increased from 0.58 ± 0.14 to 0.76 ± 0.14. Higher serum 25(OH)D was associated with lower 12-week QuickDASH after adjustment (β per 10 ng/mL = −4.04, 95% CI −7.17 to −0.91; p = 0.012). Additionally, 25(OH)D <20 ng/mL was associated with higher 12-week QuickDASH (β = 6.43, 95% CI 1.17 to 11.69; p = 0.017). Serum 25(OH)D was not clearly associated with 12-week grip strength ratio. Conclusions: Lower serum 25(OH)D, interpreted as a vitamin D nutritional-status marker rather than as a nutrition-specific causal exposure, was associated with worse 12-week patient-reported function, but not grip strength ratio. The <20 ng/mL threshold analysis was exploratory and was not powered for subgroup inference. These findings should be interpreted as observational and hypothesis-generating. Full article

Samara Oblast is an ecological transition zone in Russia, yet its spotted fever group Rickettsia (SFGR) diversity and prevalence in Dermacentor ticks remain unexplored. This study characterized SFGR species circulating in Dermacentor reticulatus and Dermacentor marginatus across 15 districts of Samara Oblast. We collected 681 adult Dermacentor ticks via vegetation flagging during 2023–2025. SFGR screening was performed via a commercial qPCR kit. Genospecies were identified via Sanger sequencing of the partial gltA gene and validated by means of ompB analysis, while tick species were confirmed using a cox1 gene fragment. The overall SFGR prevalence was 33.5% (228/681). Infection rates were significantly higher in D. marginatus (44.7%) than in D. reticulatus (27.5%). Rickettsia raoultii predominated (94.4%), while Rickettsia slovaca was relatively rare (4.6%) and significantly associated with D. marginatus. Notably, partial ompB sequencing revealed two distinct R. raoultii putative genotypes circulating in the region: one with a 9 bp deletion and one without. No coinfections were detected. Unexpectedly, a single D. reticulatus tick tested positive for Rickettsia felis, confirmed by means of gltA and ompB, marking the first molecular detection of R. felis in Russia and globally in this tick species. Samara Oblast represents a high-prevalence sympatric zone for Dermacentor-borne SFGR. The molecular detection of R. felis in D. reticulatus suggests a potential association that requires confirmation through further studies. Full article

Bovine mastitis caused by Streptococcus uberis (S. uberis) remains a major challenge of dairy production system worldwide. This study aimed to develop a colorimetric loop-mediated isothermal amplification (LAMP) assay and a conventional PCR assay targeting the 16S rRNA gene for detection of S. uberis in bovine milk. Both assays were evaluated with a simplified HotSHOT (HS) DNA preparation method that can be completed in under 10 min and was compared with a commercial DNA extraction kit before LAMP and PCR testing. LAMP reactions using HS-extracted DNA required an extended incubation time of 30 min, compared with the standard 60 min, to account for the crude DNA preparation. Using tenfold serial dilutions of purified DNA in nuclease-free water, the limit of detection was 1.84 × 10⁻⁴ ng/µL for LAMP and 1.84 × 10⁻⁵ ng/µL for PCR. In pasteurised milk spiked with S. uberis DNA and extracted by HS, the limit of detection was 10 ng/mL for LAMP and 1 ng/mL for PCR. Using the commercial kit, both methods achieved 1 ng/mL. Among 17 culture-confirmed clinical milk samples extracted by HS, LAMP detected S. uberis in 14 samples (82.35%; 95% CI: 0.56 to 0.96), while PCR detected 15 samples (88.24%; 95% CI: 0.64 to 0.99), with no significant difference between methods (McNemar’s test, p > 0.05). Both LAMP and PCR showed 100% analytical specificity against 10 non-target bacterial species under the conditions tested. These findings support HS combined with colorimetric LAMP as a practical diagnostic workflow that warrants further validation under field conditions. Full article

Background and Objectives: A subset of cancer patients treated with immune checkpoint inhibitors may experience rapid tumor progression rather than therapeutic benefit, a phenomenon described as hyperprogressive disease (HPD), which is linked to poor prognosis and shortened survival. Reliable biomarkers capable of predicting HPD remain lacking. To better understand the molecular background of HPD, we analyzed promoter region methylation and somatic mutation profiles in cancer-related genes in patients with malignant melanoma (MM) and renal cell carcinoma (RCC) undergoing anti-PD-1/PD-L1 treatment. Methods: Patients diagnosed with MM or RCC and treated with anti-PD-1/PD-L1 agents between 2011 and 2020 were included, and FFPE tumor samples along with paired normal tissues were analyzed. A diagnosis of HPD was assigned to patients with RECIST 1.1-defined progressive disease who demonstrated a ≥2-fold acceleration in tumor growth kinetics after initiation of immune checkpoint inhibitor therapy. Methylation-specific real-time PCR was performed on 54 samples (15 MM tumors, 22 RCC tumors, 17 RCC-matched adjacent normal samples) to assess promoter methylation of PIK3CA, BAP1, PTEN, and TP53. Next-generation sequencing (NGS) with an 86-gene pan-cancer panel was conducted on 9 HPD samples. Results: Promoter hypermethylation involving PIK3CA, BAP1, PTEN, and TP53 was more pronounced in HPD-associated tumor samples (n = 16) than in tumors without HPD (n = 21). Within the MM cohort, PTEN and TP53 methylation levels demonstrated statistically significant differences between the two groups (p = 0.005 and p = 0.028, respectively), while no comparable associations were observed in RCC patients. NGS analysis detected missense mutations classified as pathogenic or likely pathogenic in 5 of 9 HPD patients (55.6%), involving KIT, PTEN, and VHL. Conclusions: Promoter region hypermethylation in cancer-related genes may contribute to the aggressive tumor behavior observed in HPD. The somatic variants identified in HPD patients are consistent with known oncogenic pathways. These findings support further investigation of epigenetic and genomic biomarkers for HPD risk stratification in larger, prospective cohorts. Full article

Reusing cast-in-place (CIP) concrete elements could enhance the sustainability of the construction industry by enabling circularity, preserving embodied value, and reducing primary resource consumption, construction and demolition waste, and emissions from new concrete production. However, the implementation of such reuse is hindered by project-specific geometries, monolithic connections, and complex coordination requirements. Existing process representations address individual aspects of reuse, but an integrated process framework for coordinating assessment, dismantling, logistics, and reuse across multiple actors and projects is still lacking. To address this gap, this study develops a concept for a process-driven digital ecosystem supporting the circular reuse of CIP concrete elements within the Collaborative Research Centre 1683. Literature-based process representations are analysed, translated into Business Process Model and Notation (BPMN), and synthesised into domain-specific process models. The resulting models formalise the reuse chain, clarify actor responsibilities and information flows, and support the identification of technical, temporal, and spatial dependencies. Building on this formalisation, a conceptual digital ecosystem is derived that links information on reusable elements with process logic and reuse-related decision-making. The concept centres on a construction kit (CK) as a standardisation layer and an element data store (EDS) as the information basis for traceability, coordination, and matching. The results provide a structured foundation for digitally supported sustainability-oriented circular construction and for future ontology integration, process simulation, and decision-support applications. Full article

The complex genus Achillea L. comprises more than 140 species distributed widely throughout the Northern Hemisphere. Several species are widely used in traditional medicine for their therapeutic properties, yet few studies have correlated their biological properties with the plant’s phytochemical composition. Among these, Achillea setacea Waldst. & Kit. is a perennial species traditionally used to treat digestive and inflammatory disorders. In this study, the essential oil of A. setacea, collected wild in North Macedonia, was analyzed spectrometrically and spectroscopically by GC-MS and NMR, respectively. A total of nineteen compounds were identified, with camphor (31.3%), 4-terpineol (11.3%), and eucalyptol (10.6%) being the main constituents. Furthermore, the biological activities of pure oil were evaluated, showing notable antioxidant properties, as well as antimicrobial effects against a panel of clinically relevant microorganisms, including Gram-positive and Gram-negative bacteria. Furthermore, its impact on human intestinal epithelial (Caco-2) cells was assessed, highlighting its potential relevance for gastrointestinal applications, in agreement with the traditional use of Achillea species for digestive disorders. Full article

Human immunodeficiency virus and tuberculosis (HIV/TB) coinfection remains a major global health challenge. Immune dysregulation in HIV complicates TB diagnosis. The type of immune response mounted in tuberculosis is a key determinant in deciding the outcome of the infection. Hence, estimating immune markers is critical for developing diagnostic, monitoring and treatment approaches. A study was conducted to evaluate the diagnostic potential of host-based biomarkers in individuals with HIV/TB coinfection in comparison to HIV monoinfection receiving antiretroviral therapy. Host-based biomarkers were quantified using commercially available kits. Receiver operated curve (ROC) analysis was conducted to determine diagnostic performance. Routine investigations showed significantly raised ratios of neutrophils, monocytes, and platelets-to-lymphocytes and alkaline phosphatase levels in HIV/TB coinfection (AUC values > 0.76). Plasma galectin-9 and osteopontin levels had an AUC > 0.8. IFN-γ, TNF-α and IL-12 levels were also significantly raised (AUC values > 0.95) while levels of GM-CSF and IL-6 were significantly low in HIV TB coinfection. The ROC analysis revealed the highest diagnostic accuracy of IL-12, indicating its potential as an adjunct immunological biomarker in identifying TB among HIV-infected individuals. However, a large-scale prospective study is required to confirm the findings and to understand their role in predicting the development of tuberculosis disease in people living with HIV. Full article

Backgrounds/Objectives: Allele frequencies of genetic variants associated with complex diseases can contribute to varying degrees to predisposition depending on the population’s genetic profile. The aim of this study was to analyze the genetic diversity of 15 relevant SNVs that could modulate bone and cartilage metabolism in underrepresented structured populations. Methods: In a sample of 130 Mestizos and 304 natives from 8 native Mexican populations, SNVs related to multifactorial diseases were genotyped using a SNaPShot Multiplex kit and analyzed via capillary electrophoresis using an ABI PrismTM 3130 Genetic Analyzer (Applied Biosystems, Waltham, MA, USA.), and genetic profiles for 15 SNVs were obtained using GeneMapper software v. 3.2. Allele frequencies were calculated by locus and population using Power Stats and Arlequin v.3.1 software, for which the EM algorithm was used to compare reference populations obtained from the dbSNV database of the International HapMap project. Population structure, paired comparisons, and genetic differentiation between native, admixed, and reference populations (p value) were estimated through Fst tests using the STRUCTURE v.2.3.2 and Arlequin v.3.1 software. Results: Haplotype frequency combinations grouped as profiles showed higher predominance in the allelic combination A/A/G for rs9340799 (ESR1), rs700518 (CYP19A1), and rs1800795 (IL6) genes, respectively. Conclusions: Allelic profiles could be useful as medical tools for preventing and managing individuals or populations. Mexican populations showed high genetic variability among allelic risk profiles for estrogen control and response, as well as high frequencies of variant combinations associated with an increased inflammatory response, potentially resulting in high osteoclastogenesis. This analysis advances our understanding of the complexity of bone and cartilage metabolism in highly stratified populations. Full article

Background/Objectives: We aimed to conduct a comprehensive assessment of how transient iatrogenic hypothyroidism, induced for diagnostic purposes during the follow up of patients with differentiated thyroid cancer, impacts both quantitative and qualitative lipid parameters. Methods: Blood samples were collected during continuous levothyroxine (LT4) supplementation and after four weeks of LT4 withdrawal. In addition to thyroid hormone levels and routine lipid parameters, LDL and HDL subfractions were analyzed using polyacrylamide gel electrophoresis (Lipoprint). Furthermore, the activities of HDL-associated human paraoxonase-1 (PON1) paraoxonase and arylesterase were measured spectrophotometrically, while the levels of myeloperoxidase and apolipoprotein M (ApoM) were determined using ELISA. The activity of key regulators in HDL remodeling was measured using activity assay kits. Results: In this prospective, single-center study, a total of 52 patients were enrolled (mean age 48 ± 15 years; 13 males and 39 females). Compared to values measured during continuous LT4 supplementation, total cholesterol, HDL-C, LDL-C, ApoA1, and ApoB100 levels were significantly elevated during iatrogenic hypothyroidism (p < 0.0001 for all parameters). Differences in lipoprotein subfraction patterns were also observed: in hypothyroidism, the mean LDL particle size decreased (p = 0.0007) and the proportion of HDL subfractions shifted to the larger HDL subfractions (p < 0.0001). The paraoxonase activity and ApoM level tended to be increased (p = 0.030 and p = 0.011, respectively). Conclusions: In short-term overt hypothyroidism, opposing changes were observed: the shift toward smaller, denser LDL subfractions is considered atherogenic, whereas the increased proportion of larger HDL subfractions, the trend for higher paraoxonase activity and apoM levels can be potentially anti-atherogenic. Our findings further characterize the functional alterations of lipoproteins in hypothyroidism. Full article

Antimicrobial resistance is increasing, necessitating the development of novel and efficacious therapies. Plants contain phytochemicals, some of which may possess antibacterial properties. This research employed broth dilution experiments to investigate the antibacterial efficacy of fifteen phytochemicals identified in medicinal plant extracts. The sum of fractional inhibitory concentration of phytochemicals in conjunction with reference antibiotics were also analysed. The inhibitory effects of phytochemicals against β-lactamase were evaluated to explore their potential mechanisms of action. The phytochemicals were evaluated for toxicity on human dermal fibroblast cells. Gallic acid and luteolin significantly inhibited Staphylococcus aureus and the methicillin-resistant S. aureus (MRSA) strain, with minimum inhibitory concentration (MICs) of 62.5 µg/mL. Gallic acid also demonstrated restricted efficacy against Gram-negative species, with MICs ranging from 312.5 to 1250 µg/mL. Gram-negative bacteria exhibited no response to luteolin. Ellagic acid, catechin, naringenin, and quercetin exhibited moderate antibacterial efficacy against the tested pathogens (625–2500 µg/mL MIC). Corilagin exhibited significant antibacterial activity against S. aureus and MRSA, with a MIC of 7.81 µg/mL. Corilagin also exhibited notable efficacy against Bacillus cereus, Shigella flexneri, and Klebsiella pneumoniae, with MICs ranging from 62.5 to 250 µg/mL. Fractional inhibitory concentration studies revealed a synergistic effect between amoxicillin and corilagin against B. cereus. Additionally, catechin, luteolin, and quercetin synergised penicillin G against S. aureus. Quercetin potentiated the activity of β-lactams (amoxicillin, penicillin G, and oxacillin) against MRSA. Notably, these antibiotics were ineffective against MRSA alone. Isobologram analysis revealed potentiation between penicillin G and quercetin against MRSA at all tested ratios. The β-lactamase inhibitory activity of the phytochemicals was evaluated using a commercial screening kit, and the percentage of relative inhibition was determined. Quercetin and luteolin both inhibited β-lactamase, achieving relative inhibition rates of 77–100% across two time intervals. All phytochemicals were nontoxic against human dermal fibroblasts. Indeed, quercetin enhanced cell survival by 200%. Full article

This study validated immunoassays for measuring circulating DHEA and DHEA-S in broiler plasma and compared the two biomarkers. A commercially available RIA kit for DHEA and a species-independent ELISA kit for DHEA-S were tested against each other and available literature data. Blood samples were collected from 68 female broilers at slaughter. Most sample concentrations were close to the lower calibration range. DHEA concentrations ranged from 52 to 354 pg/mL, whereas DHEA-S values ranged from 76 to 7320 pg/mL. Both assays showed satisfactory validation results, including good precision (intra- and inter-assay CV ≤ 15%), accuracy (recovery ≥ 99%), linearity (R² > 0.9; run test p > 0.1), and parallelism between calibrator curves and sample dilutions (ANCOVA p > 0.1). However, the DHEA-S assay showed high cross-reactivity with DHEA (160%), making quantitative DHEA-S determination unreliable; therefore, values should be interpreted as an estimate of combined DHEA/DHEA-S concentrations. Consequently, the higher concentrations measured with the DHEA-S ELISA compared with the DHEA RIA (Bland–Altman bias: −525.8 pg/mL) do not indicate a true predominance of DHEA-S. Nevertheless, both assays may represent useful tools for comparative evaluations among samples, although they do not provide reliable information on the physiological interconversion between the two steroids. Full article

Neutralizing antibodies (NABs) play a critical role in assessing the immune response elicited by vaccines, providing insight into their protective efficacy. Despite their importance, there is a notable gap in research directly comparing NAB levels among individuals vaccinated with different vaccines, across diverse ethnicities, and between genders. The study aimed to compare NAB levels across variables such as vaccination status, vaccine type, age, gender, and ethnicity. The NAB levels among different study groups were measured using the Finecare RBD Antibody Test and the cPass kit (ELISA). The data was analyzed statistically using SPSS version 27. A total of 172 study subjects were analyzed. The mean age of participants was 45.03 ± 16.72 years, with 50.9% male and 77.3% of Malay ethnicity. Median NAB levels, assessed by both assays, were highest in females, vaccinated healthy participants, and those who received the Pfizer vaccine. Age-group comparisons revealed variations in median NAB levels across studied groups. Participants aged 10–25 years in the vaccinated healthy (VH) group exhibited the highest median antibody levels; on the other hand, the 26–45 year age group showed the highest median levels in the breakthrough infection (BI) and certain non-vaccinated categories. Ethnic group comparisons highlighted that Malays consistently had the highest median NAB levels. Significant differences in antibody levels were found across vaccination status, ethnicity, and vaccine type (p < 0.001). This study underscores the influence of vaccination status, demographic factors, and vaccine type on NAB levels. The Finecare RBD Antibody Test and cPass kit demonstrated comparable trends, highlighting their utility in evaluating vaccine-induced immunity. The findings of this study highlight the need for tailored immunization strategies to optimize protective immunity. Full article