Search Results (378)

Background/Objectives: Nutraceuticals containing milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are purported to abate age-related metabolic dysfunction due to their richness in milk sphingolipids. As such, nutraceuticals offer a compelling strategy to improve metabolic health through dietary means, especially for elderly persons who are unable to adhere to common therapeutic interventions. To address this, we examined the effects of supplementing aged sedentary rats with an MFGM/EV-rich concentrate. Methods/Results: In a 25-week study, 89-week-old male rats received either a milk sphingolipid-rich MFGM/EV concentrate or a control supplement. Analysis of metabolic health using a battery of tests, including MS^ALL lipidomics of plasma, liver, and other peripheral tissues, revealed that MFGM/EV supplementation promotes accretion of unique sphingolipid signatures, ameliorates ceramide biomarkers predictive of cardiovascular death, and has a general lipid-lowering effect. At the functional level, we find that these health-promoting effects are linked to increased lipoprotein particle turnover, showcased by reduced levels of triglyceride-rich particles, as well as a metabolically healthier liver, assessed using whole-body lipidomic flux analysis. Conclusions: Altogether, our work unveils that MFGM/EV-containing food holds a potential for ameliorating age-related metabolic dysfunction in elderly individuals. Full article

Domain-Specific Languages with JSON grammar (JSON-DSLs) are specialized programming languages tailored to specific problem domains, offering higher abstraction levels and simplifying software implementation through the JSON standard. RhoArchitecture is an approach for designing and executing JSON-DSLs, incorporating a modular programming model, a JSON-based evaluation engine, and an integrated web development environment. This paper presents RestRho, a RESTful NodeJS server developed using two JSON-DSLs designed with RhoArchitecture: SQLRho and DBRestRho. These languages enable declarative specification of database operations and HTTP requests, respectively, supporting modularity, reuse, and template-based transformations. We validate the RestRho implementation through a dual approach. First, we apply software metrics to assess code quality, maintainability, and complexity. Second, we conduct an empirical study involving 39 final-year computer engineering students, who completed 18 structured tasks and provided feedback via questionnaires. The results demonstrate the tool’s usability, development efficiency, and potential for adoption in web application development. Full article

Background and Aims: Sepsis-associated acute kidney injury (S-AKI) is common and is associated with poor outcomes. This prospective observational study aimed to assess the predictive value of four novel biomarkers—syndecan-1 (SDC1), neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin (PENK), and presepsin (PSPN)—for renal outcomes and mortality in septic ICU patients. Methods: Serum biomarker levels were measured in serum samples collected at the time of sepsis diagnosis on the basis of the Sepsis-3 criteria. Acute kidney injury (AKI) was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, and patients were grouped by the presence of AKI, renal replacement therapy requirement (RRT), and intensive care unit (ICU) survival. Demographic, clinical, laboratory, and severity score data were compared between groups to evaluate the predictive performance of biomarkers and clinical parameters. Results: Of the 140 septic patients included, 55.0% developed AKI, 17.2% required RRT, and the ICU mortality rate was 50.0%. SDC1 was independently associated with both AKI (OR: 1.201; p = 0.024) and RRT initiation (OR: 1.260; p = 0.004). It also demonstrated the highest predictive performance for RRT (AUC: 0.715; p = 0.001) and a significant AUC for AKI evaluation (AUC: 0.659; p = 0.002). NGAL levels were significantly elevated in patients with AKI and higher SOFA scores but were not independently predictive. PENK and PSPN were not significantly associated with any renal outcome or mortality. The combined SOFA–SDC1 model improved discrimination for both AKI (AUC: 0.770) and RRT (AUC: 0.737), surpassing individual predictors. Conclusions: SDC1 emerged as the most reliable biomarker for assessing AKI and predicting the need for RRT, highlighting its potential role in early renal risk stratification among critically ill patients. Full article

Background: Gait impairments are common in individuals with knee osteoarthritis awaiting total knee arthroplasty, affecting their mobility and quality of life. This study aimed to assess and compare biomechanical gait features between individuals awaiting total knee arthroplasty and healthy, non-arthritic controls, focusing on less-explored variables using sensor-based measurements. Methods: A cross-sectional observational study was conducted with 60 participants: 21 individuals awaiting total knee arthroplasty and 39 nonarthritic controls aged 64–85 years. Participants completed a standardized 14 m walk, and 17 biomechanical gait parameters were measured using the BTS G-Walk inertial sensor. Key variables, such as stride duration, cadence, symmetry indices, and pelvic angles, were analyzed for group differences. Results: The pre-total knee arthroplasty group exhibited significantly longer gait cycles and stride durations (p < 0.001), reduced cadence (p < 0.001), and lower gait cycle symmetry index (p < 0.001) than the control group. The pelvic angle symmetry indices for tilt (p = 0.014), rotation (p = 0.002), and obliquity (p < 0.001) were also lower. Additionally, the pre-total knee arthroplasty group had lower propulsion indices for both legs (p < 0.001) and a lower walking quality index on the right leg (p = 0.005). The number of elaborated steps was significantly greater in the pre-total knee arthroplasty group (left, p < 0.001, right: p < 0.001). No significant differences were observed in any other gait parameters. Conclusions: This study revealed significant gait impairment in individuals awaiting total knee arthroplasty. Although direct evidence for prehabilitation is lacking, future research should explore whether targeted approaches, such as strengthening exercises or gait retraining, can improve gait and functional outcomes before surgery. Full article

Follicular lymphoma (FL) is one of the most common types of non-Hodgkin’s lymphomas. The tumor is characterized by a wide range of clinical manifestations, ranging from indolent forms to early transformation and progression with a poor prognosis. The search for clinically significant genetic changes is essential for personalized risk assessment and treatment selection. The CREBBP gene is frequently mutated in this type of lymphoma, with changes occurring at the level of the earliest tumor precursor cells. However, the prognostic and diagnostic significance of the CREBBP gene mutation status in FL has not been fully established. In this study, we analyzed sequencing data of exons 22–30 of the CREBBP gene in 86 samples from patients with different grades of FL (1–3B), including those in the 3A–3B subgroup without the t(14;18) translocation. We also investigated the prognostic significance of CREBBP gene mutations in relation to the treatment options, namely high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT/auto-HSCT) and conventional chemotherapy programs (CCT). It was found that FL patients with a single missense mutation in the KAT domain of the CREBBP gene experienced an extremely low number of early adverse events related to lymphoma and had better long-term survival rates, regardless of treatment option. In contrast, when comparing patients with FL without a missense mutation in the KAT domain or those with multiple mutations in the CREBBP gene, overall and progression free survival were worse, and early progression and histological transformation were more common. Compared to standard therapy, patients who underwent HDCT/auto-HSCT in the FL 1–3B (14;18)-positive group without a single missense mutation in the KAT domain had better survival rates and lower rates of transformation and early progression. In addition, among patients with FL 3A–3B (14;18)-negative, we found that there were no cases of a missense mutation in the KAT domain of the CREBBP gene. This suggests that a single missense mutation in the CREBBP gene may be a feature that discriminates 14;18-positive FL with a favorable prognosis from a high-risk disease. FL 3A–3B (14;18)-negative may represent a distinct variant with different biology and underlying mechanisms of development compared to classical FL. Full article

Aurora kinase B (AURKB), a serine/threonine protein kinase, is essential for accurate chromosome segregation and cytokinesis during mitosis. Dysregulation of AURKB, often characterized by its overexpression, has been implicated in various malignancies, including breast cancer. However, the mechanisms governing its dysregulation remain incompletely understood. Here, we identify a pivotal role for the MOF/MSL complex—which includes the histone acetyltransferase MOF (KAT8)—in modulating AURKB stability through acetylation at lysine 215 (K215). This post-translational modification inhibits AURKB ubiquitination, thereby stabilizing its protein levels. MOF/MSL-mediated AURKB stabilization promotes the proper assembly of the chromosomal passenger complex (CPC), ensuring mitotic fidelity. Notably, inhibition of MOF reduces AURKB K215 acetylation, leading to decreased AURKB expression and activity. Consequently, this downregulation suppresses expression of the downstream oncogene c-MYC, ultimately attenuating the malignant proliferation of breast cancer cells. Collectively, our findings reveal a novel mechanism by which lysine acetylation regulates AURKB stability, highlight the significance of the MOF-AURKB-c-MYC axis in breast cancer progression, and suggest potential therapeutic strategies targeting this pathway in clinical settings. Full article

Shaker K⁺ channel proteins are responsible for potassium (K⁺) uptake and transport, playing a critical role in plant growth, development, and adaptation to K⁺ deficiency. Cassava, a key tropical root crop, is known for its characteristic of resilience to nutrient-poor soil and drought stress. However, the Shaker K⁺ channel gene family in cassava has not yet been characterized. In this study, 13 Shaker channel genes were identified from the near telomere-to-telomere (T2T) cassava genome using bioinformatics analysis. Phylogenetic relationships classified these genes into five distinct subfamilies, and all encoded proteins contained the conserved GYGD/GYGE motif typical of Shaker channels. Protein interaction network predictions revealed potential interactions among the Shaker family, as well as with the potassium transporter HAK5. Tissue-specific expression pattern analysis showed that MeGORK and MeAKT1.2 were expressed in all tissues. Furthermore, quantitative real-time PCR (qRT-PCR) analysis was conducted to examine the transcriptional levels of Shaker K⁺ channel gene family members in the roots and leaves of two cassava germplasms with different low-potassium tolerance after one month of low-potassium treatment. The results revealed that MeAKT1.2, MeAKT2.2, and MeKAT1 exhibited distinct expression patterns between the two germplasms, with higher expression levels observed in the potassium-tolerant germplasm. Therefore, these three genes may serve as important candidate genes for potassium stress tolerance in cassava. In summary, this study provides valuable insights into the characteristics and biological functions of the Shaker K⁺ channel gene family in cassava and identifies potential candidate genes for breeding or engineering potassium-efficient cassava cultivars. Full article

In a previous article, an estimation procedure for calculating the liquidus and solidus lines of binary equilibrium phase diagrams was presented. In this article, keeping the thermodynamic basics, the estimation method for the approximate calculation of the liquidus and solidus surfaces of ternary phase diagrams was further developed. It is shown that the procedure has a hierarchical structure, and the ternary functions contain the binary functions. The applicability of the method is checked by calculating the liquidus and solidus surfaces of the Ag-Au-Pd isomorphous ternary equilibrium phase diagram. The application of each level of the developed four-level procedure depends on the data available and the aim. It is shown that in the case of a concentration range close to the base alloy pure element, the liquidus and solidus surfaces of the ternary equilibrium phase diagram can be calculated from the liquidus and solidus functions of the binary equilibrium phase diagrams with a few K errors, which is 0.2 at% at 10 K/at% slope. The equilibrium phase diagrams were available in graphical form, so the data obtained via digitalisation of the diagrams for the calculations was used. The functions describe the slope of the surfaces, and the approximate method developed for the calculation of the partition ratios is also shown. Full article

This study aimed to investigate population genetic differences related to reproductive traits between Duroc and Yorkshire (Dutch Large White) pigs using two approaches: linear mixed models that dissect additive and dominant effects, and selective sweep analysis. (1) Methods: Genome-wide single-nucleotide polymorphism (SNP) data of 3917 Duroc and 3217 Yorkshire pigs were analyzed. The first principal component (PC1) was used as a simulated phenotype to capture population-level variance. Additive and dominant genetic effects were partitioned and evaluated by using the combination of the linear mixed models (LMM) and ADDO’s algorithm (LMM + ADDO). In parallel, selective sweep signals were detected using fixation index (F_ST) and nucleotide diversity (θ_π) analyses. A comparative assessment was then conducted between the LMM + ADDO and the selective sweep analysis results. Significant loci were annotated using quantitative trait loci (QTL) databases and the Ensembl genome browser. (2) Results: There are 39040 SNPs retained after quality control. Using the LMM + ADDO framework with PC1 as a simulated phenotype, a total of 632 significant SNPs and 184 candidate genes were identified. Notably, 587 SNPs and 171 genes were uniquely detected by the LMM + ADDO method and not among loci detected by the top 5% of F_ST and θ_π values. Key candidate genes associated with litter size included HSPG2, KAT6B, SAMD8, and LRMDA, while DLGAP1, MYOM1, and VTI1A were associated with teat number traits. (3) Conclusions: This study demonstrates the power of integrating additive and dominant effect modeling with population genetics approaches for the detection of genomic regions under selection. The findings provide novel insights into the genetic architecture of reproductive traits in pigs and have practical implications for understanding the inheritance of complex traits. Full article

The increasing release of nanoparticles into aquatic environments, particularly via wastewater, raises concerns about their biological effects on microbial communities. This study investigated the molecular response of Pseudomonas putida to aluminum oxide nanoparticles (Al₂O₃NPs) under controlled conditions and in synthetic wastewater, both before and after biological treatment. Acute toxicity was evaluated using growth inhibition assays, while the expression of katE, ahpC, and ctaD—genes associated with oxidative stress and energy metabolism—was quantified via RT-qPCR. Exposure to pristine Al₂O₃NPs induced a strong, time-dependent upregulation of all tested genes (e.g., katE and ahpC up to 4.5-fold). In untreated wastewater, this effect persisted but at a lower intensity; bulk Al₂O₃ caused only moderate changes. Treated wastewater samples showed markedly reduced gene expression, indicating partial detoxification. Nanoparticles elicited stronger biological responses than their bulk counterparts, confirming the material form-specific effects. Comparative analysis with Daphnia magna revealed similar patterns of oxidative stress gene activation. These findings highlight the influence of nanoparticle form and environmental matrix on microbial responses and support the use of gene expression analysis as a sensitive biomarker for nanoparticle-induced stress in environmental risk assessment. Full article

Background/Objectives: Patellar instability in adolescents is a significant cause of short- and long-term morbidity and disability. Traditionally, patients with first-time patellar dislocation are managed nonoperatively, although most studies are not focusing on the adolescent athletic population. The primary objective of the current study was to compare patient-reported outcomes and complications in adolescent athletes who underwent surgery either after the first patellar dislocation or after the recurrence of the dislocation with a minimum postoperative follow-up of 48 months (48–75 months). Methods: A total of 39 adolescent athletes who underwent medial patellofemoral ligament (MPFL) reconstruction (Group A, after the first dislocation, and Group B, recurrent patella dislocation) were included in this study. In all the patients, the same MPFL reconstruction technique was applied using a semitendinosus autograft. The graft was fixed on the patella using a transverse tunnel and adjustable loop button fixation and, in the femur, using a tunnel and absorbable screw fixation. The tunnel was drilled obliquely to prevent penetration of the distal femoral physis. The preoperative and postoperative clinical and functional evaluations of the patients were conducted via the visual analog scale (VAS), the Lysholm Knee Scoring System, the Kujala Anterior Knee Pain Scale, and the Pediatric International Knee Documentation Committee (Pedi-IKDC), and the return to sports score was assessed via the Tegner Activity Scale (TAS). Results: At the latest follow-up, both groups demonstrated significant improvement in the Lysholm scores, with Group A achieving a mean of 92.57 ± 6.21 and Group B achieving a mean of 90.53 ± 8.21 (p = 0.062). Postoperatively, Group A achieved a mean Kujala score of 94.21 ± 9.23, whereas Group B reached 92.76 ± 12.39, with no statistically significant difference (p = 0.08). The Pedi-IKDC score improved postoperatively in both groups. In Group A, it increased from 67.98 ± 12.29 to 93.65 ± 4.1, and in Group B, from 56.21 ± 13.6 to 91.67 ± 6.21 (p = 0.067). The preoperative visual analog scale (VAS) score for pain was significantly lower in Group A (3.1 ± 1.13) than in Group B (4.2 ± 3.01, p < 0.01). At the latest follow-up, the VAS scores improved in both groups, with Group A reporting a mean score of 0.47 ± 1.01 and Group B 0.97 ± 1.32 (p = 0.083). The Tegner activity scores were similar between the groups preoperatively, with Group A at 7.72 ± 1.65 and Group B at 7.45 ± 2.09 (p = 0.076). Postoperatively, Group A had a mean score of 7.28 ± 2.15, whereas Group B had a mean score of 6.79 ± 3.70 (p = 0.065). The mean time to return to sports was significantly shorter in Group A (5.1 ± 1.3 months) than in Group B (7.6 ± 2.1 months) (p < 0.01). Overall, 84.61% of the patients returned to their previous activity level. Specifically, 95.2% (20/21) of patients in Group A achieved this outcome, whereas 72.22% (13/18) achieved it in Group B. Patient satisfaction was generally high, with 76% (16/21) of patients in Group A reporting being satisfied or very satisfied, compared with 77% (14/18) in Group B. Conclusions: MPFL reconstruction is a safe and effective procedure for both acute and recurrent patellar dislocation in adolescent athletes. While patients who underwent acute reconstruction returned to sport more quickly and showed higher absolute postoperative scores, the greatest overall improvement from preoperative to final follow-up was observed in those treated for recurrent instability. Both surgical approaches demonstrated high satisfaction rates and minimal complications, supporting MPFL reconstruction as a reliable option in both acute and recurrent cases. Full article

Gender-independent, intersex, non-binary, and transgender (GIaNT) youth have puberty health and sex education needs that are different from cisgender youth. Unfortunately, this population has historically been excluded from curricula pertaining to these issues in schools throughout the U.S. and Canada. While sex education programs are limited for all youth, and navigating puberty can range from exciting to scary for all youth, GIaNT youth are particularly vulnerable to facing negative outcomes by being omitted from such curricula. Because they are not able to access adequate information in schools and in their family/friend networks, a majority of GIaNT youth turn to the internet to seek out resources for education on puberty health and sex education. To this end, our team is in the process of creating an online educational resource (OER) that is age-appropriate and affirming for GIaNT youth to be provided with resources that are personalized to users’ unique needs. This literature review discusses content suggestions for inclusion of comprehensive puberty health and sex education that caters to GIaNT youth and their unique needs. Full article

Cold Shock Proteins (Csps) are multifunctional regulators critical for bacterial stress adaptation. While Csps are known to regulate biofilm formation and low-temperature growth in some species, their roles in mycobacteria remain unclear. Here, we explored the functions of three Csps (CspA1, CspA2, and CspB) in Mycobacterium smegmatis. We found that CspA1 promotes biofilm formation and isoniazid (INH) resistance but negatively affects oxidative stress resistance. In contrast, CspB promotes biofilm formation, whereas CspA2 appears functionally redundant in this process. Notably, CspB and CspA2 do not contribute redundantly to oxidative stress resistance. Proteomic analysis revealed that CspA1 significantly modulates the expression of key metabolic and stress-response proteins, including WhiB3 and KatG. Our findings establish CspA1 as a key regulatory factor in mycobacteria, linking metabolic adaptation to biofilm-associated drug resistance and oxidative defense. Full article

Objectives: The incidence of postoperative pain in patients that undergo spinal interventions is significantly increased, affecting their functional outcomes and quality of life. Dexmedetomidine (DEX) belongs to the category of centrally acting nonopioid agents with highly selective α2 adrenoreceptor agonist activity that are frequently applied in spinal surgery based on its antinociceptive and anxiolytic properties. Although many studies displayed the effectiveness of DEX in postoperative pain management, the impact of DEX on functional improvement after spinal surgeries is still debatable. Purpose: This systematic review focuses on the intraoperative and postoperative role of dexmedetomidine (DEX) as an analgesic agent in elective and emergency adult spine surgery. Methods: An electronic literature review search was conducted via Web of Science and PubMed to assess the impact of DEX on postoperative pain management, postoperative delirium (POD), and postoperative cognitive dysfunction (POCD). Discussion: Twenty-one studies were retrieved, three of which were review articles. The effects of DEX were studied for up to 48 h postoperatively. In most cases, its administration was associated with reduced intraoperative and postoperative opioid consumption. However, findings on pain control were less conclusive due to heterogeneity in dosing protocols, concomitant medications, the timing of administration, and pain scoring systems. DEX appears to reduce the incidence of POD and POCD, particularly when used in combination with other drugs. Conclusions: Although the present study supports that the intraoperative administration of dexmedetomidine decreases the pain intensity and/or opioid consumption as well as the development of POD and POCD in patients undergoing spinal surgeries during the first 24 h postoperatively, the current literature should be expanded to allow for the safe generalisation of findings over longer follow-up periods. Further research into the neuroprotective, analgesic, and anti-inflammatory roles of DEX is warranted. Full article

Background: Metabolic syndrome and Parkinson’s disease have common pathophysiological denominators. This study aimed to investigate how metabolic syndrome contributes to Parkinson’s disease progression, as well as the genetic traits shared by PD and MetS. Methods: Four hundred and twenty-three newly diagnosed drug-naïve PD patients were analyzed from the Parkinson’s Progression Markers Initiative (PPMI) database. We compared longitudinal changes in the total and subscale scores of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) between PD patients with and without metabolic syndrome over a five-year follow-up. We assessed the frequency of PD-associated genetic variants in both groups. Results: At baseline, Parkinson’s patients with MetS were typically men (p < 0.01) and older (p = 0.04), with a higher Hoehn and Yahr score (p = 0.01) compared with their counterparts without MetS. They showed higher Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total scores at baseline and in follow-up years 2, 3, 4, and 5 (all p-values < 0.05) as analyzed by the Generalized Estimating Equation model. These differences were primarily driven by elevated motor scores (MDS-UPDRS Part III) (p < 0.01). MetS was associated with a higher frequency of the ZNF646.KAT8.BCKDK_rs14235 variant and a lower frequency of the NUCKS1_rs823118 and CTSB_rs1293298 variants. Conclusions: PD patients with MetS had worse motor symptomatology. Both conditions appear to share genetic susceptibility, involving genes related to lipid metabolism (BCKDK), autophagy and inflammation (CTSB), and chromatin regulation (NUCKS1). Full article