Search Results (350)

Since January 2023, the Russian Federation has implemented expanded neonatal screening for 36 hereditary disorders, which has changed the diagnostic algorithm for hyperphenylalaninemia/phenylketonuria (HPA/PKU) by introducing tandem mass spectrometry (MS/MS) on the second day of life, followed by confirmatory biochemical and molecular testing in newborns at risk. We analyzed 1247 newborns aged 5–15 days with elevated phenylalanine levels (≥120 µmol/L) and a phenylalanine to tyrosine ratio of at least 1 detected during the first stage of screening using MS/MS. At the reference center, newborns underwent repeat biochemical testing and stepwise molecular analysis of HPA-associated genes. Two pathogenic variants in HPA-associated genes were identified in 538 newborns, including 534 newborns with biallelic pathogenic variants in PAH and 4 with BH4-deficient forms (PTS, QDPR). The incidence of molecularly confirmed HPA was 1:4518 newborns (95% CI: 1:4152–1:4925). The PAH variant spectrum was dominated by p.Arg408Trp (c.1222C>T) (33.4%). Genotype-based analysis indicated that 73 newborns (13.7%) were likely responsive to cofactor therapy, whereas 222 (41.6%) were potentially responsive. These findings define the molecular epidemiology of HPA in Russia and support early genetic stratification for diagnosis and treatment. Full article

This study proposes a hybrid machine learning model based on full-spectrum pulsed neutron logging data to address the monitoring challenges of Carbon Capture, Utilization, and Storage (CCUS) under complex geological conditions. Traditional interpretation models for sequestered CO₂ saturation (e.g., macroscopic capture cross-section model, characteristic peak count model, and ratio model) heavily rely on prior parameters such as porosity, formation water salinity, and lithology. Acquiring these parameters in real time during practical engineering is often costly and difficult. To reduce the rigid dependence of accurate CO₂ saturation monitoring on complex prior parameters like porosity and salinity under heterogeneous geological settings, this research focuses on the Pearl River Mouth Basin, a core carbon sequestration target area in the Guangdong-Hong Kong-Macao Greater Bay Area, based on the evaluation results of offshore carbon sequestration macro-regions in China. Taking the primary reservoirs of the Enping and Wenchang Formations as typical geological prototypes, a high-fidelity, full-spectrum neutron–gamma response database was constructed using Monte Carlo simulations. Two machine learning strategies are proposed: a direct regression model (NMF+SVR) and a joint model (NMF+SVC/KMeans+SVR). Based on Monte Carlo simulated data, experimental results demonstrate that, compared with traditional petrophysical baseline models and simple machine learning models, the proposed joint learning method effectively reduces the dependence of CO₂ saturation monitoring on lithology and porosity. Furthermore, it is proven that even with a single-detector tool configuration, the method exhibits high prediction accuracy under complex lithological conditions. Notably, the two-step joint model achieves a Root Mean Square Error (RMSE) as low as 4.200%, significantly outperforming traditional physics-based models and single machine learning models such as MLP and RF. This study provides a physically interpretable and accurate technical reference for applying machine learning to pulsed neutron-logging-based CO₂ geological sequestration monitoring. Full article

Background: Phenylketonuria (PKU) is a rare genetic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, resulting in a deficiency of the enzyme responsible for metabolizing phenylalanine (Phe) and its accumulation. PKU can be identified through newborn screening (NBS) or genetic sequencing; however, both approaches have limitations, including high false-discovery rates and variants of uncertain significance (VUS). This study aims to identify a PKU metabolomic profile using unique biomarkers to enhance early diagnosis and improve treatment outcomes. Methods: Dried blood spot (DBS) samples from 65 patients diagnosed with PKU and matched healthy controls were collected through the NBS program. An untargeted metabolomics analysis was conducted using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to profile metabolites and investigate altered metabolic pathways in patients with PKU. Results: A total of 418 significantly dysregulated metabolites were identified in PKU patients. Among them, 90 metabolites were identified as endogenous human metabolites. The most significantly affected pathways were those related to the metabolism of aromatic amino acids and polysaccharides. Moreover, lipid metabolic pathways were dysregulated, including those involved in fatty acid and phospholipid biosynthesis. In addition to phenylalanine (AUC = 0.994), 1,11-Undecanedicarboxylic acid (UDCA) (AUC = 0.969) was significantly elevated in patients with PKU, suggesting it is a promising potential biomarker for PKU. Conclusions: Untargeted metabolomics revealed distinct metabolic alterations in patients with PKU, providing insights into disease pathophysiology. The identification of UDCA as a consistently elevated metabolite supports its potential utility as a supplementary biomarker for PKU diagnosis and monitoring. Further validation in larger cohorts, using a targeted metabolomics approach, is warranted. Full article

Background: Dietary management of phenylketonuria (PKU) focuses on restricting phenylalanine (Phe) intake. The European PKU guidelines and the PKU Dietary Handbook recommend a simplified PKU diet, allowing unrestricted consumption of many low-Phe foods, called free foods. While this approach may reduce the treatment burden for patients, its implementation varies. This study investigated practices of Swedish metabolic dietitians regarding the simplified diet and the use of free foods for classical PKU (cPKU) and compared these with European recommendations. Methods: A survey was distributed to all metabolic dietitians in Sweden. The survey included questions on professional experience, the use of free foods and the classification of 135 low-protein food items as never, sometimes or always counted in cPKU. Data were summarised descriptively. Results: All 13 eligible dietitians participated. The use of free foods was recommended by 8/13 dietitians. Of foods classified as free in the PKU Handbook, about one third were commonly restricted in Swedish PKU practice. For 39% of the foods surveyed, no single response option (never, sometimes or always counted) reached >50%, indicating variation in practice. Classification of individual foods partially aligned with their Phe content, but portion size and concerns about excessive Phe intake also influenced advice. Conclusions: Significant variation exists in the dietary management of PKU in Sweden, and the simplified diet approach is not consistently implemented. Dietitians’ concerns about the safety of increased Phe intake from free foods play a central role in this. These findings highlight challenges in incorporating international guidelines into national practice and underscore the need for further research to address dietitians’ safety concerns related to the simplified diet. Full article

Background/Objectives: Biological factors such as genetics contribute to nutrition-related outcomes, but nutritional epidemiological studies often lack consideration of genetics despite evidence of their functional impacts on health and cognition. Phenylalanine hydroxylase (PAH) genetic variation has been hypothesized to influence health and cognitive outcomes due to evidence of metabolic perturbations in L-phenylalanine to L-tyrosine hydroxylation, including plausible downstream effects on catecholamine neurotransmitters among not only individuals with phenylketonuria (PKU) [homozygotes for PAH mutations] but also PKU carriers [heterozygotes]. Related to these metabolic perturbations, diminished executive functioning has been observed in individuals with PKU, even when treated, but research is lacking exploring this outcome in PKU carriers. The present study aims to detail methods for stratifying populations based on genetic variation, for use in epidemiological precision nutrition research. It further provides an exploratory exemplar of such research through population stratification by PAH genetic variation (i.e., PKU carriers vs. non-carriers), while providing the first descriptive data on executive functioning skills using the validated Executive Skills Questionnaire—Revised (ESQ-R) tool with PAH-genetically stratified groups (PKU carriers and non-carriers). Methods: Participants were ≥18 years of age and PAH heterozygotes (PKU carriers) or non-carriers. Levels of executive functioning were self-reported anonymously online and included the validated Executive Skills Questionnaire—Revised (ESQ-R) tool. Data were analyzed using t-tests, chi-square tests, ANOVAs, and ANCOVAs. Results: Respondents (n = 99, n = 79 carriers and n = 20 non-carriers) consisted of males (22.2%) and females (77.8%), primarily of European ancestry. There were no significant differences between groups (carriers vs. non-carriers) for total scores (mean ± SD ESQ-R score carriers = 17.41 ± 14.01; non-carriers = 14.95 ± 10.00), but carriers scored significantly worse than non-carriers for the ESQ-R item “I have trouble making a plan” in the adjusted model. Conclusions: This study provides a methodological exemplar for exploring genetically stratified subpopulations in epidemiological precision nutrition research. Full article

Background/Objectives: Phenylketonuria (PKU) is a rare autosomal recessive disorder caused by phenylalanine hydroxylase (PAH) deficiency, impairing the conversion of phenylalanine (Phe) to tyrosine. Although early diagnosis and intervention yield excellent outcomes, dietary adherence often declines in adulthood, potentially leading to poor metabolic control and adverse nutritional consequences. This study aimed to evaluate physical activity levels, nutritional status, metabolic control, and anthropometric outcomes in adults with classic PKU, which have not been sufficiently researched in the current literature. Methods: This cross-sectional study included 100 adults with classical PKU (cPKU; baseline phenylalanine levels ≥ 1200 µmol/L) under regular follow-up at the Division of Metabolism, Hacettepe İhsan Doğramacı Childrens’ Hospital. Sociodemographic traits and dietary behaviors were evaluated through structured interviews carried out by a dietitian. Dietary intake was assessed by using a 24 h dietary recall method, and nutrient analyses were performed with the Bebis 7.2 software program. Using the short version of the International Physical Activity Questionnaire (IPAQ), physical activity levels were specified, and participants were categorized according to established scoring criteria. Results: A hundred adults with classical PKU took part in the study, including 47 males and 53 females, with a mean age of 23.84 ± 5.41 years; 5% of participants were underweight, 40% had normal weight, 39% were overweight, and 16% were listed as obese. The intake of mean daily energy is 2443.8 ± 384.6 kcal for men and 1822.5 ± 312.7 kcal for women. Carbohydrates contributed approximately 61% of total daily energy intake in both genders, whereas protein accounted for 12–13% and fat for approximately 26–27% of total energy intake; 17% of participants were physically inactive, 40% were minimally active, and 43% met criteria for sufficient physical activity according to IPAQ-based classification. Energy intake, the use of Phe-free protein substitutes, and BMI were significantly higher in the sufficiently active group compared to the low-active group in men, while no significant differences were observed between physical activity groups among women. Conclusions: Adults with classical PKU showed a high prevalence of overweight and obesity, together with differences in dietary intake and physical activity patterns. Physical activity levels were associated with several nutritional and metabolic characteristics; however, further long-term research is required to fully understand these connections. Full article

Background: Phenylketonuria (PKU) is a metabolic disorder requiring a strict low-phenylalanine diet. Oral health impairment, including bacteriome dysbiosis, is common in PKU, yet the mycobiome remains poorly defined. This pilot study aimed to characterise the salivary oral mycobiome of children with PKU compared with controls and to explore associations with dietary intake. Methods: Saliva samples from 18 children, including 8 patients with PKU and 10 age-matched controls, were profiled using internal transcribed spacer (ITS) amplicon sequencing. Alpha/beta diversity, taxonomic composition, diet–fungi correlations, discriminative taxa and LEfSe were analysed. Results: Alpha diversity did not differ significantly between groups after correction for multiple comparisons, although exploratory subgroup analyses suggested lower evenness in PKU children aged <10 years compared with older controls. Beta diversity differed by diagnosis (PERMANOVA: F = 1.7251, p = 0.0062) and in the age–diagnosis model (F = 1.8502, p = 0.0004). Taxonomic analyses identified nominal differences in several fungal taxa, including Candida (p = 0.011), Saccharomycetales_fam_Incertae_sedis (p = 0.011), Naganishia (p = 0.020), and Aspergillaceae (p = 0.036) in PKU samples; however, these findings should be interpreted as exploratory because many did not remain significant after FDR correction. Diet–mycobiome analyses identified selected FDR-supported associations, including an inverse relationship between phenylalanine intake and Naganishia in PKU. Conclusions: This pilot study suggests preliminary compositional differences in the oral mycobiome of children with PKU that may be related to dietary therapy and metabolic context. These exploratory findings require validation in larger cohorts with detailed oral health assessment and control of confounders. Full article

Carbon nanotube field-effect transistors (CNT FETs) hold great promise for extending Moore’s Law, yet their performance is critically limited by excessive off-state leakage, caused by band-to-band tunneling (BTBT) in narrow bandgap CNT channels. In this work, we overcome this long-standing bottleneck by introducing a co-design strategy that integrates a small-diameter HiPco CNT channel with a novel asymmetric gate architecture. This approach strategically reshapes the channel electrostatics to simultaneously suppress the gate-induced drain leakage (GIDL) effect and preserve excellent carrier transport. The efficacy of this strategy is rigorously validated through calibrated technology computer-aided design (TCAD) simulations for both NMOS and PMOS operation, demonstrating an ultralow off-current of 10 fA/µm, an on-current of 1.08 mA/µm, and a record on–off ratio of 1.1 × 10¹¹ for back-gated CNTFETs at the 90 nm node. The design exhibits outstanding scalability: at the scaled 28 nm node with a supply voltage of 0.7 V, the PMOS device achieves 3 mA/µm on-current and 6 pA/µm off-current, maintaining an on–off ratio of 5 × 10⁸. This work establishes a scalable pathway toward femtoampere-level CNT CMOS, addressing the static power challenge in future nano-electronics. Full article

The dependence of electronic products on printed circuit boards (PCBs) is increasing. In recent years, PCB defect detection technology has achieved considerable results, but the defect targets are small, the background is complex, and there are many integrated components, which poses great challenges to product quality control. Therefore, this paper proposes a printed circuit board defect detection network that integrates coordinate attention and multi-level gradient flow optimization, called EP-YOLO, to improve the detection accuracy of printed circuit board defects. Firstly, this paper improves the model’s ability to capture small target details by reconstructing the detection head of the small target. Based on this, a Shallow Context Feature Extraction (SCFE) network is designed to fuse shallow features with multi-scale features, effectively preventing the loss of shallow detail information and texture features. At the same time, in order to suppress background noise, this paper designs a multi-level feature gradient flow optimization module (C2f_CA, abbreviated as CCA) that integrates coordinate attention and a Cross-Stage Partial Frequency-domain Omni-Kernel module (CSPFOK) to enhance feature extraction capability. Finally, the SCYLLA-IoU (SIoU) optimization model training process was introduced. The experimental results showed that EP-YOLO achieved 97.5% mAP50 on the PKU-Market-PCB dataset and 98.5% mAP50 on the DeepPCB dataset, with a parameter reduction of approximately 12.55%, outperforming popular object detection networks. The results highlight the potential capabilities of EP-YOLO, providing a powerful and effective solution for industrial PCB defect detection. Full article

Background: Sapropterin allows dietary liberalisation in responsive individuals with phenylketonuria (PKU), increasing natural protein intake and reducing dependence on protein substitutes (PSs). As PSs provide essential micronutrients, dietary liberalisation may increase the risk of nutritional insufficiency. Evidence describing detailed micronutrient intake in sapropterin-treated children remains limited. Methods: This secondary analysis evaluated dietary protein and micronutrient intake after 24 months of sapropterin treatment in 21 responsive children from a prospective longitudinal study. Caregiver-completed three-day food records were analysed for protein, calcium, iron, zinc, vitamin D, and vitamin B₁₂, with micronutrient intakes compared with UK dietary reference values (DRVs). Results: Mean total protein intake was 75 ± 14 g/day, comprising 30 ± 16 g/day natural protein and 45 ± 21 g/day protein equivalent from PSs; natural protein tolerance ranged from 8 to 66 g/day. PSs contributed most micronutrients: calcium 80%, iron 84%, zinc 87%, vitamin D 96%, and vitamin B₁₂ 78%. Median micronutrient intakes exceeded DRVs for most children; however, four had intakes below DRVs, almost exclusively when PSs were reduced or omitted. One child consuming >40 g/day natural protein without PSs had low iron (51%), zinc (90%), and vitamin D (4%) intakes. A non-adherent adolescent had low intakes of calcium (46%), iron (64%), zinc (41%), and vitamin D (60%). Another child receiving 60 g/day protein equivalent from PSs had marginally low vitamin D intake (85%) due to lower fortification. Children maintaining regular PS use met micronutrient requirements. Conclusions: After two years of sapropterin treatment, dietary liberalisation increased natural protein intake but did not consistently ensure adequate micronutrient intake. Micronutrient shortfalls were associated with reduced PS use, emphasising the need for careful dietitian-guided adjustment as diets become more flexible. Full article

Discrete memristive chaotic maps are promising for secure communications due to their digital compatibility, yet existing designs face limitations, including narrow hyperchaotic ranges and a single type of chaotic attractor. This paper proposes a family of 2D hyperchaotic maps by coupling a discrete exponential memristor with four 1D seed maps. Theoretical analysis reveals that the exponential memristor induces non-hyperbolic fixed points and periodicity with respect to the memristor’s initial charge, enabling controlled coexistence of both homogeneous and heterogeneous multistable attractors. Numerical simulations show two positive Lyapunov exponents (LEs) and broad hyperchaotic regions; the memristor-coupled Sine map achieves a maximum LE of 0.4963 and spectral entropy (SE) of 0.8915, outperforming representative cosine- and quadratic-based benchmarks. A pseudorandom number generator (PRNG) passes all National Institute of Standards and Technology (NIST) SP 800-22 tests. STM32F407-based hardware experiments confirm physical realizability, and an image encryption application demonstrates near-ideal entropy (7.9883) and strong differential attack resistance. These results establish the discrete exponential memristor as an effective nonlinearity for enriching chaos complexity and hardware-oriented security primitives. Full article

Phenylketonuria (PKU) is an autosomal recessive disorder characterised by an inborn error of phenylalanine (Phe) metabolism. Such errors are attributed to pathogenic gene variants causing phenylalanine hydroxylase (PAH) deficiency, impairing the hydroxylation of phenylalanine to tyrosine in the Phe metabolic pathway. This defect leads to plasma Phe concentrations above the normal range. If untreated, hyperphenylalaninemia can adversely affect brain function, leading to severe intellectual disability and seizures. Since 1969, the newborn dried blood spot test has remained the main method of early screening and diagnosis for PKU. The primary therapeutic management is a lifelong phenylalanine-restricted diet with the aim of decreasing plasma Phe levels. The recommended diet consists of avoiding high-protein foods such as meat, fish, eggs and nuts, and can be supplemented with high-protein medical formulas which are low in phenylalanine. Pharmacological interventions such as sapropterin, sepiapterin and pegvaliase can also be used as treatment adjuncts in patients with PKU. Currently, small-molecule inhibitors reducing renal phenylalanine reabsorption are being explored as a potential therapeutic intervention. Furthermore, novel gene-editing techniques are under evaluation as potential curative strategies, with preclinical studies showing promising results in correcting pathogenic phenylalanine hydroxylase variants. This non-systematic review synthesises current literature on the management of PKU, with a focus on dietary interventions and recommendations. Full article

As the cornerstone of contemporary electronics, the quality of electronic substrates—including Printed Circuit Boards (PCBs) and Ceramic Package Substrates (CPSs)—is intrinsic to product reliability. However, automated inspection is currently impeded by two persistent obstacles: the drastic multi-scale variation in defects and the acute class imbalance within defect datasets. Conventional deep learning approaches often fail to reconcile these challenges simultaneously, leading to suboptimal recognition of rare defect categories. To bridge this gap, we propose Multi-scale Partial Vision Transformer—Simple, Parameter-free Attention Module (MulPViT-SimAM), a robust framework designed for class-imbalanced electronic substrate defect detection. Our method features a novel multi-scale backbone (MulPViT) that synergizes partial convolutions with hierarchical attention mechanisms, facilitating the efficient extraction of both fine-grained local textures and global contextual dependencies. Additionally, we embed the Simple, Parameter-free Attention Module (SimAM) into the feature fusion stage to adaptively highlight defect-specific features while dampening background noise. To further mitigate data imbalance, we utilize the Equalized Focal Loss (EFL) function, which employs a category-specific modulating factor to dynamically equilibrate the learning focus across different classes. Comprehensive benchmarking reveals state-of-the-art performance, achieving mAP@0.5 scores of 95.7% on the standard PKU-MARKET-PCB dataset and 54.2% on the highly challenging CPS2D-AD dataset. Significantly, our approach effectively mitigates class imbalance, narrowing the performance deviation of rare categories to just 4.3% on the PKU-Market-PCB dataset and 1.4% on the CPS2D-AD dataset, compared to 11.8% and 7.5% in baseline models. These findings position MulPViT-SimAM as a viable and efficient solution for industrial quality control. Full article

PCB surface defect detection plays a critical role in ensuring electronics manufacturing quality. To address the challenges of small target defect detection, this study proposes PCB-YOLO, an enhanced lightweight detector based on YOLOv8n. PCB-YOLO introduces three key improvements. First, a RepViT-EMA Fusion Architecture (REFA) module is designed for deep backbone layers to strengthen feature extraction while suppressing background interference from complex circuit patterns. Second, a Multi-Scale Grouped Aggregation (MSGA) module is developed to reduce feature redundancy and improve spatial-semantic information extraction for multi-scale defects. Third, a Pixel-level Intersection over Union (PIoU) loss function is proposed to enable pixel-level IoU calculation with enhanced angular and area constraints for more precise localization. Extensive experiments on the PKU-Market-PCB dataset demonstrate that PCB-YOLO achieves 98.4% mAP@0.5, 97.4% recall, and 96.1% precision with only 2.4 M parameters, 6.9 G FLOPs, and an inference speed of 224 FPS, outperforming multiple state-of-the-art methods while maintaining real-time capability. Additional experiments on the DeepPCB dataset yield 99.0% mAP@0.5 and 80.4% mAP@0.5:0.95, confirming the cross-dataset generalization ability of the proposed method. Full article

Background/Objectives: In Phenylketonuria (PKU), engaging in regular physical activity and exercise (PA/E) is important for physical and psychological health, but additional considerations may be required to facilitate uptake and performance as well as to optimise metabolic control. The aim of this study, therefore, was to investigate the stakeholder perspectives on the barriers, facilitators, and solutions to completing PA/E, sport, and nutrition in PKU. Methods: In total, 7 in-person and 6 online semi-structured focus groups (FGs) were conducted with individuals with PKU (n = 31), caregivers (n = 13), clinicians (n = 17), and medical industry professionals (n = 14) in PKU (n = 75 total participants). Three main questions about the barriers, facilitators, and solutions to performing PA/E with PKU were explored. Identified themes were mapped onto the capability, opportunity, motivation, and behaviour (COM-B) model of behaviour change with anonymous quotes from relevant stakeholders used to illustrate the findings. Results: Five common themes were identified. Most notably, individuals with PKU and their caregivers stated fatigue, poor recovery, low energy, and fear around the impact of exercise on blood phenylalanine (Phe) control were barriers to PA/E. Individuals with PKU were aware of the potential benefits of exercise, stating PA/E impacted positively on their mental well-being, daily functioning, and happiness and improved their self-confidence and long-term health. Identified solutions to PA/E participation included greater knowledge in regard to the impact of PA/E on Phe levels, improvements in advice on amount and supplementation with protein substitutes, tailored PKU nutritional advice, more awareness of PA/E within and outside the PKU community, specific PKU guidelines for PA/E, more scientific research, and PA/E events. Misalignment was evident, such that individuals with PKU reported additional barriers to PA/E, whereas other key stakeholder groups perceived the same barriers as the general public. Conclusions: There seems to be a misalignment between individuals with PKU, caregivers, clinicians, and industry professionals regarding PA/E, sport, and nutrition. Individuals with PKU and caregivers reported additional barriers to undertaking PA/E, sport, and nutrition compared to the general public. This suggests that further education and collaboration is needed through stakeholders to better understand how such barriers could be overcome in respect of PA/E, sport, and nutrition in individuals with PKU. Full article