Search Results (12,494)

Background: Haemoglobinopathies such as beta-thalassemia (β-thal), alpha-thalassemia (α-thal) and sickle cell disease (SCD) are characterised by pathogenic gene variations (mutations) in the globin genes. Patients with haemoglobinopathies have the same disease-causing coding variations with very different disease phenotypes, from requiring blood transfusions to being non-symptomatic. The gap between the expected clinical outcomes based on primary coding mutations (the genotype) and the actual observed symptoms (the phenotype) often remains unexplained. We refer to the contribution of secondary genetic modifiers—specifically, non-coding variants of the genome that alter globin gene expression and pathophysiology—as the “missing heritability” of the clinical presentation [Primary Mutation + Missing Heritability (Non-Coding Variants) = Actual Clinical Phenotype]. Objectives: This systematic review aims to find evidence connecting genetic differences outside of the protein-coding region, as in promoters, enhancers or untranslated regions (UTRs), to the clinical severity (phenotype) of beta-thalassemia, alpha-thalassaemia and SCD. We summarise the molecular basis of phenotypic variation among haemoglobinopathy patients with identical variations to reveal their missing heritability and to enhance our understanding of prognostic strategies. Methods: This systematic review was performed in accordance with the PRISMA 2020 guidelines. We used search terms related to haemoglobinopathies, non-coding variation, SNP, promoters, enhancers and clinical severity to search major databases (PubMed and Google Scholar) as of October 2025. A total of 527 (out of 572) abstracts were fit for initial screening to identify the eligible reports. Due to heterogeneity in study designs and reported outcomes, findings were synthesised descriptively and grouped by variant mechanism (cis-acting and trans-acting). The final analysis included 89 articles that demonstrated a direct association between a non-coding genomic variant and a quantitative measure of clinical severity. Results: Two main groups of non-coding variants (NCVs) that modulate foetal haemoglobin (HbF) induction were identified. The first major group comprises cis-acting variants within globin gene clusters (HBG2 promoter XmnI polymorphism, HBB promoter mutations and α-globin enhancer variants), while the second major group comprises trans-acting quantitative trait loci (QTLs) (BCL11A and HBS1L-MYB loci). Non-globin NCVs in the UGT1A1 promoter were also found to influence the severity measures in β-thal and SCD. NCVs primarily alter the binding of transcription factors and the looping dynamics of chromatin, modulating the α/β chain balance ratio and γ-globin repression. The XmnI polymorphism is the most prominent cis-acting modifier associated with β-thal intermedia. The promoter polymorphisms in TNF-α and VCAM1 are associated with vascular complications in SCD. Conclusions: NCVs are fundamental when determining the clinical measures of haemoglobinopathies, in addition to coding variants. NCV screening should be integrated for clinical prognosis for the accurate prediction of haemoglobinopathy severity and associated high-risk complications. NCVs may represent promising targets for next-generation gene editing and therapeutic intervention strategies aimed at modifying the severity of β-thal, α-thal and SCD. Full article

This research studied the role of the fisheries sector, specifically pond-based grouper aquaculture, in coastal Lamongan, Indonesia, which is crucial for coastal food security and economy. Despite relatively high productivity, technical efficiency was not optimal because of its limited livelihood assets, which include human, natural, social, financial, and physical capital. The gap in ownership of these assets has resulted in technical efficiency variations across farmers and has affected both their livelihoods and environmental sustainability. Previous research has mostly focused on capture fisheries or non-grouper species, leaving a critical gap regarding the linkage between livelihood assets and technical efficiency in pond-based grouper aquaculture. This research measured livelihood asset levels, technical efficiency, and the effect of assets on efficiency, using quantitative data from 83 respondents representing the total 105 grouper farming households in coastal Lamongan. Livelihood assets were assessed through scoring and index analysis, technical efficiency was estimated using Stochastic Frontier Analysis (SFA), and the determinants of inefficiency were examined through Tobit regression with robust standard errors. The results found that the average livelihood asset index was 0.47 (moderate), with financial capital being the weakest component. Technical efficiency averaged 0.83, indicating efficient use of inputs while still allowing room for improvement. Natural capital (land area and water resources) and financial capital (income and savings) significantly affected technical inefficiency, whereas human, social, and physical capital did not. These findings emphasize the importance of strengthening the financial capital and the management of natural resources optimally to promote the efficiency and sustainability of grouper aquaculture in coastal Lamongan, Indonesia. Full article

To address the issues of displacement and insufficient positional stability observed in the clinical use of the PROPEL Mini stent, this study investigates the influence of different biodegradable materials on the mechanical properties of the stent under the constraint of a fixed monofilament braided closed-loop geometry. Finite element analyses are conducted using Abaqus/Explicit to quantitatively evaluate the nonlinear mapping between nominal diameter, axial length, and radial pressure throughout a loading–unloading cycle. The results reveal that while axial behavior is consistent during compression, material-specific plasticity causes irreversible geometric sets in Mg alloy and PLGA models, whereas the PCL stent achieves total elastic recovery to its initial dimensions. During unloading, the Mg alloy stent recovers to a nominal diameter of 28 mm with a reduced axial length of approximately 22 mm, whereas the PLGA stent exhibits a much smaller recovery diameter of 14 mm with an axial length of approximately 23 mm. These post-release configurations directly determine the functional expansion range of the biodegradable stents after implantation. During unloading, the Mg alloy stent provides the highest radial pressure (peak 6.8 kPa) with a functional recovery range up to 26.5 mm, ensuring superior scaffolding stability. In contrast, while PCL achieves the widest recovery (52 mm), its radial pressure is clinically negligible (the maximum value is still less than 165 Pa), and the PLGA model exhibits both insufficient support and a restricted functional recovery limit (13 mm). By using high-strength materials such as Mg alloys, the radial anchoring force of the stent can be effectively enhanced without changing the existing structure, providing a scientific basis for solving clinical displacement problems. Full article

Remote and hybrid teaching have become enduring features of European higher education, yet their implications for teachers’ well-being are often examined in fragmented ways. This study investigated a systemic imbalance across five interdependent domains—physical, emotional, cognitive, social, and existential well-being—among Lithuanian higher education teachers, interpreted through the Job Demands–Resources framework and Self-Determination Theory. Using a mixed-methods design, data were collected from 385 teachers via a structured online questionnaire that included demographic variables, 10-point imbalance ratings across the five domains, and open-ended questions. Quantitative analyses (descriptive statistics and correlational pattern exploration) were complemented by thematic analysis of teachers’ narratives. Results indicate a widespread multidimensional disruption: elevated stress and emotional exhaustion, substantial physical strain associated with inadequate home workspaces, cognitive overload linked to multi-platform teaching, reduced collegial connection, blurred work–life boundaries, and challenges to professional meaning. Strain was unevenly distributed, with higher vulnerability associated with gender and caregiving demands, early-career status, limited ergonomic conditions, and weak institutional support. The findings support a systemic interpretation in which intensified demands, reduced resources, and frustrated psychological needs jointly drive well-being imbalance. Sustainable remote/hybrid teaching therefore requires institution-level measures (workload regulation, training, ergonomic support, and boundary-setting policies) rather than reliance on individual coping alone. Full article

Spent coffee grounds are an abundant agro-industrial by-product with considerable potential as a functional food ingredient. This study investigated the effects of lactic acid fermentation on the antioxidant and anti-inflammatory activities of spent coffee grounds, as evaluated using their extracts, with a focus on fermentation-induced remodeling of phenolic compounds and the functional implications. Fermentation was conducted using Lactobacillus plantarum, and changes in microbial growth, pH, reducing sugar content, phenolic composition, antioxidant capacity, and anti-inflammatory activity were evaluated. During fermentation, viable cell counts increased from 6.73 log colony-forming units (CFU)/mL at 0 h to 9.27 log CFU/mL at 48 h, accompanied by a decrease in pH and an increase in reducing sugar content, indicating active microbial metabolism. Total polyphenol content increased markedly, reaching 97.44 mg gallic acid equivalents (GAE)/100 g in water extracts fermented for 48 h compared with 62.96 mg GAE/100 g in non-fermented controls. High-performance liquid chromatography analysis revealed significant enrichment of phenolic acids, including caffeic, ferulic, and protocatechuic acids. Correspondingly, fermented extracts exhibited enhanced antioxidant activities, as determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), superoxide dismutase (SOD-like, and catalase assays. In addition, fermented extracts showed improved cellular compatibility and significantly inhibited nitric oxide production (approximately 50–60% at 200–300 μg/mL) and pro-inflammatory cytokine production, with interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) inhibition rates exceeding 60% at 200–300 μg/mL in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. These biological effects were closely linked to fermentation-induced qualitative and quantitative changes in phenolic composition, providing mechanistic insight beyond simple activity enhancement. Overall, lactic acid fermentation enhances the functional properties of spent coffee grounds, highlighting their potential as upcycled, value-added ingredients for functional food and nutraceutical applications. Full article

Building height is a critical parameter for urban analysis, yet accurately estimating it from ICESat-2 photon-counting LiDAR data remains challenging due to pervasive noise photons and uneven noise distribution. To address the limitations of fixed-threshold denoising methods and improve adaptability across varying density conditions, this study proposes a dual-stage denoising framework for ICESat-2 ATL03 photon data. In the first stage, local photon densities are estimated within a reliable radius, log-transformed, and stratified into multiple levels. Adaptive thresholds are then applied at each level to suppress low-density noise while minimizing over-filtering in sparse regions. In the second stage, residual feedback-driven adaptive fitting strategy is applied along the ground track, where polynomial fitting was performed in sliding windows, with the window size dynamically adjusted based on residuals to refine local structures and eliminate outliers. The experiment was conducted in South Holland and Friesland, across 84 ICESat-2 tracks, where quantitative evaluations under varying day/night and beam conditions confirmed the effectiveness of the proposed framework. For denoising, the proposed method achieved high denoising accuracy, with F1-scores exceeding 0.97 in most cases, outperforming previous methods. Furthermore, building heights derived from footprint buffering and elevation differencing are validated against airborne LiDAR, yielding coefficient of determination (R²) values of 0.7235 and 0.9487 for the two regions, with root mean square error (RMSE) values of 1.5045 m and 1.8849 m, respectively. This study confirms the effectiveness and robustness of the proposed dual-stage framework, demonstrating its strong capability for both noise suppression in ICESat-2 ATL03 photon data and the subsequent accurate estimation of building heights. Full article

Background: Brace adherence is a key determinant of treatment success in adolescents with idiopathic scoliosis. However, adherence is influenced by multiple clinical, psychological, and social factors, and reported wear times vary widely across studies. This systematic review and meta-analysis aimed to identify determinants of brace adherence and assess their quantitative impact on real wear. Methods: A comprehensive search was conducted in PubMed/MEDLINE, Scopus, Web of Science, Embase, and Google Scholar from database inception to November 2025. A total of 1040 records were identified, 620 were screened, and 45 full-text articles were assessed for eligibility. In total, 17 studies met the inclusion criteria and were included in the qualitative synthesis, and 10 provided extractable quantitative data and were included in the meta-analysis. A random-effects model was used to calculate pooled mean differences for identified determinants, including sex, age, early adherence, and sensor-based monitoring. Results: In total, 17 studies involving 1716 adolescents were included, and 10 provided extractable quantitative data for meta-analysis. Objective sensor-based monitoring was consistently associated with higher adherence, with a pooled mean difference of 25.6 percent compared with non-sensor methods. Early adherence significantly predicted long-term compliance, with a mean difference of 9.6 percent. Younger adolescents demonstrated greater adherence than older patients, with a mean difference of 19.1 percent, while sex differences favored females but did not reach statistical significance. Psychosocial determinants such as body image perception, stress, family dynamics, and religious environment played an important role in modulating adherence. Higher body mass index (BMI) and reduced quality of life were associated with poorer compliance. Overall, studies evaluating positive determinants reported a pooled mean adherence of 89.6 percent compared with 67.7 percent in studies characterized by negative determinants. Conclusions: Brace adherence is determined by a combination of clinical and psychosocial factors. Sensor-based monitoring, strong early adherence, and supportive environments consistently enhance compliance, whereas stress, poor body image, and higher BMI hinder wear. Targeted interventions, early counseling, and standardized adherence metrics are needed to improve outcomes in brace-treated scoliosis. Full article

Background: The emergence of polymyxin-resistant, carbapenem-resistant Klebsiella pneumoniae (CRKP) presents a critical challenge to clinical management. This study aimed to delineate the molecular mechanisms driving the acquisition of polymyxin resistance in CRKP. Methods: We analyzed polymyxin-susceptible and polymyxin-resistant CRKP isolates obtained from a single patient. Antimicrobial susceptibility testing was performed to determine the minimum inhibitory concentrations. Whole genome sequencing was employed to identify variations in two-component systems and to screen for mcr genes, which were involved in polymyxin resistance. Differential gene expression was assessed using RNA sequencing and validated by quantitative real-time PCR. Furthermore, site-directed mutagenesis was utilized to confirm the causal role of specific mutations in conferring the resistant phenotype. Results: An L96P mutation in the PhoQ protein was found in the polymyxin-resistant CRKP isolate. Compared with the PhoQ wild-type, this mutation significantly upregulated expression of phoP/Q, pmrD, and arnBCADTEF operon-related genes. A corresponding L96P mutant was subsequently constructed in the polymyxin-susceptible ATCC 13883 strain via site-directed mutagenesis. Antimicrobial susceptibility testing confirmed that the PhoQ L96P mutation elevates the minimal inhibitory concentrations of colistin and polymyxin B to 64 mg/L and >32 mg/L, respectively, from a baseline of 0.5 mg/L. Conclusions: The PhoQ L96P mutation is a pivotal driver of polymyxin resistance in CRKP, primarily mediated through the upregulation of the arnBCADTEF operon. Full article

Handheld laser-induced breakdown spectroscopy (hLIBS) can be considered one of the most recent techniques for rock characterization in situ. Handheld LIBS devices are useful tools for providing “fit for purpose” qualitative and quantitative geochemical data. The analytical performance of hLIBS instruments varies significantly between similar instruments from different manufacturers. This study employed two commercial hLIBS instruments, both making use of noise reduction and multivariate partial-least-squares (PLS) calibration. Model validation was performed using the Leave-One-Out Cross-Validation (LOOCV) method. The Random Forest (RF) and Artificial Neural Network (ANN) algorithms were also employed as complementary approaches to PLS modeling, with the goal of exploring potential nonlinear relationships between spectral intensities and reference analyte concentrations. A comparison was also made with the most basic and commonly used approach, univariate analysis, demonstrating that multivariate methods achieve superior performances. To evaluate the predictive performance and quantification capability of the acquired LIBS spectra, the Pearson’s coefficient (R²) and root-mean-square error (RMSE) were employed in the analysis of 21 diverse certified geochemical reference materials (CRMs). The results achieved suggested that the spectral resolution was the key factor determining the performance of multivariate LIBS calibrations. The PLS model proved to be satisfactory for analyses performed by the higher-spectral-resolution instrument, whereas complementary algorithms were necessary to achieve better results with the lower-spectral-resolution instrument. Full article

Two methods (macroscopic and quantitative histology) to determine sexual maturity are described in this paper, with an emphasis on the methods used in stereology. Based on a point counting grid (Glagolev’s method), ovarian cellular structures were quantified throughout the whole cross section of 151 Pleuronectes platessa individuals. The novelty of this paper is checking the cellular homogeneity in the anterior, median and posterior sections of both ovaries from 15 fish, accompanied by a reading protocol to limit subjectivity during stereology readings. Once the ovarian structures were quantified for 151 individuals, a model was set up following the standardized staging grid of the International Council for the Exploration of the Sea (ICES), classifying each sampled individual into a maturity phase. These results showed that 23.4% of the time immature (A) individuals were correctly identified through the macroscopic method, but 47.9% of developing (B) individuals were classified under A, while individuals that had finished spawning were correctly identified as such 80.4% of the time. Finally, the maturity ogive and the length at which 50% of the population is sexually mature (L₅₀) were calculated, with an L₅₀ of 28.6 cm when using the macroscopic method and an L₅₀ of 20.6 cm with the stereological method. Full article

Background: The Balance Error Scoring System (BESS) is the most practiced static postural balance assessment tool, which relies on visual observation, and has been adopted as the gold standard in the clinic and field. However, the BESS can lead to missed and inaccurate diagnoses—because of its low inter-rater reliability and limited sensitivity—by missing subtle balance deficits, particularly in the athletic population. Smartphone technology using motion sensors may act as an alternative option for providing quantitative feedback to healthcare clinicians when performing balance assessments. The primary aim of this study was to explore the discriminative validity of an alternative novel smartphone-based cloud system to measure balance remotely in soccer athletes with and without hip pain. Methods: This is an exploratory cross-sectional study. A total of 64 Australian soccer athletes (128 hips, 28% females) between 18 and 40 years completed single and tandem stance balance tests that were scored using the modified BESS test and quantified using the smartphone device attached to their lower back. An Exploratory Factor Analysis (EFA) and a Clustered Receiver Operating Characteristic (ROC) using an Area Under the Curve (AUC) were used to explore the discriminative validity between the smartphone sensor system and the modified BESS test. A Linear Mixed-Effects Analysis of Covariance (ANCOVA) was used to determine any statistical differences in static balance measures between individuals with and without hip-related pain. Results: EFA revealed that the first factor primarily captured variance related to smartphone measurements, while the second factor was associated with modified BESS test scores. The ROC and the AUC showed that the smartphone sway measurements in the anterior–posterior and mediolateral directions during single-leg stance had an acceptable to excellent level of accuracy in distinguishing between individuals with and without hip-related pain (AUC = 0.72–0.80). Linear Mixed-Effects ANCOVA analysis found that individuals with hip-related pain had significantly less single-leg balance variability and magnitude in the anteroposterior and mediolateral directions compared to individuals without hip-related pain (p < 0.05). Conclusion: Due to the ability of smartphone technology to discriminate between individuals with and without hip-related pain during single-leg static balance tasks, it is recommended to use the technology in addition to the modified BESS test to optimise a clinician-led assessment and to further guide clinical balance decision-making. While the study supports smartphone technology as a method to assess static balance, its use in measuring balance during dynamic movements needs further research. Full article

This study describes a single-laboratory validation of an ultra-high-performance liquid chromatographic (UHPLC) method for the determination of key compounds like hericenones, hericenes, erinacines, and ergosterol in Hericium erinaceus (H. erinaceus, Lion’s Mane) raw materials and finished products. The expanding market for Hericium erinaceus (Lion’s Mane) has increased the need for practical, routine-ready analytical methods that can quantify characteristic marker compounds and strengthen quality control across both raw materials and finished products. In this study, an ultra-high-performance liquid chromatographic (UHPLC) separation method was developed for the determination of hericenones, hericenes, erinacines, and ergosterol in Hericium erinaceus raw materials and finished products. Under the optimized conditions, the major target analytes—hericenones, hericenes, erinacine A, and ergosterol—were fully resolved (R_s > 1.5) within 38 min using an HSS T3 column at 30 °C. All the peaks in the LC chromatogram of Hericium erinaceus samples and standard solutions were structurally confirmed by LC–UV-MS/MS based on the possible mass spectra. The quantitative calibration curves were linear, covering a range of 10–300 μg/mL for hericenone C, D and E, and hericene A, D and C; 3–100 μg/mL for deacylhericenone and deacylhericene; 1–50 μg/mL for erinacine A, and 5–200 μg/mL for ergosterol. Limits of quantification (LOQs) for hericenone C, D, and E and for hericene A, D, and C were approximately 9.263, 4.545, 4.650, 1.854, 10.72, and 11.18 µg/mL, respectively, while LOQs for deacylhericenone and deacylhericene were 1.083 and 2.109 µg/mL. Erinacine A and ergosterol showed LOQs of 0.642 and 8.352 µg/mL, respectively. The recovery of ergosterol was evaluated for the method at two different levels: 91.6~93.9% for 0.2% spiking and 93.0~102.6% for 0.08% spiking. The method was successfully validated, demonstrating inter-day Relative Standard Deviation (RSD) values between 1.1% and 5.7% for detected analytes across diverse matrices. This validated method provides a consistent quantification of hericenones, hericenes, erinacine A, and ergosterol across a range of commercial products and raw Hericium erinaceus materials, providing a sensitive and reliable tool for product characterization and quality control. This method provides QC laboratories with a robust, UV-based tool for standardized product characterization without requiring mass spectrometry. Full article

The pursuit of disabled students’ inclusion in higher education remains a significant global concern, particularly in developing nations where systemic and institutional barriers persist. Despite progressive legislative and policy frameworks promoting inclusive education, Kenyan and Pakistani universities continue to encounter structural, financial, and attitudinal challenges that hinder equal participation in learning and research for disabled students. This study aims to identify, analyze, and prioritize the complementary support strategies necessary for disabled students’ inclusion in learning and research opportunities in both Kenyan and Pakistani higher education institutions. Employing a quantitative research design, data were gathered through structured questionnaires distributed among disabled students in institutions of higher learning. The data were analyzed using the fuzzy synthetic evaluation (FSE) approach, which integrates fuzzy logic with descriptive statistics to objectively determine the weight, level of agreement, and internal consistency of the identified support strategies. Among the six support strategies, Physical Facility Support emerged as the most crucial in Pakistan, followed by Attitudinal and Community Support. On the other hand, the Kenyan group indicated Policies and Advocacy as the most essential support strategy for disabled students’ inclusion in higher education. The findings underscore that the two countries differ in how they prioritize support strategies for the inclusion of students with disabilities. This study contributes theoretically by advancing the application of the FSE model within inclusion research, offering a rigorous, data-driven framework for understanding multidimensional support strategies for disabled students. Full article

The clinical efficacy of chemotherapy against rapidly proliferating cells stimulates both the development of new agents and the reassessment of established drugs. Spectroscopic methods (UV, FT-IR, and ¹H NMR) were applied to characterize prospidium chloride and related substances. The FT-IR spectrum of prospidium chloride, arising from vibrational transitions within the alkyl fragments of the dispirotripiperazinium cation, is reported with band assignments. Electronic transitions between molecular orbitals are analyzed using quantum–mechanical selection rules (Laporte and spin selection rules). The n→σ* transition (ΔS = 0) corresponds to the absorption maximum at λmax = 282 ± 0.40 nm (ε = 3.89 ± 0.08 L·mol⁻¹·cm⁻¹). A ¹H NMR spectrum (700 MHz) was used to assign chemical shifts δ (ppm), J-coupling constants (Hz), and gauche conformational features of prospidium chloride and its dihydroxy and epoxy impurities. Quantitative ¹H NMR (qNMR) was applied to determine the content of the active pharmaceutical ingredient and related substances. The methods provide complementary structural information for the characterization of prospidium chloride. Full article

Natural preservation technologies have emerged as sustainable alternatives for maintaining the postharvest quality of fresh products. This study developed and characterized edible films and coatings produced from purple corn flour (MMH) and ethanolic propolis extract (EEP), and evaluated their effectiveness in extending the shelf life of Fuerte avocado. Film-forming solutions were prepared using three MMH/EEP formulations (100/0, 90/10, and 80/20), and their apparent viscosity was determined. Films obtained by drying at 45 °C for 12 h were analyzed for pH, thickness, tensile strength, solubility, water vapor permeability, and microstructure by SEM. The MMH 80/20 EEP formulation showed the best overall performance and was selected as a coating for avocados stored under ambient and refrigerated conditions. Shelf life was defined based on quantitative criteria, including acceptable limits of weight loss and sensory acceptability. Under these criteria, coated avocados reached a shelf life of 30 days at ambient temperature, compared to 15 days for uncoated fruit, and 72 days under refrigerated storage, compared to 50 days for the control. Additionally, the coating reduced weight loss, preserved moisture, and improved sensory acceptance. Overall, MMH/EEP systems represent a promising natural alternative for the postharvest preservation of avocado. Full article