Network Models of BACE-1 Inhibitors: Exploring Structural and Biochemical Relationships.

This study investigates the clustering patterns of human ß-secretase 1 (BACE-1) inhibitors using complex network methodologies based on various distance functions, including Euclidean, Tanimoto, Hamming, and Levenshtein distances. Molecular descriptor vectors such as molecular mass, Merck Molecular Force Field (MMFF) energy, Crippen partition coefficient (ClogP), Crippen molar refractivity (MR), eccentricity, Kappa indices, Synthetic Accessibility Score, Topological Polar Surface Area (TPSA), and 2D/3D autocorrelation entropies are employed to capture the diverse properties of these inhibitors. The Euclidean distance network demonstrates the most reliable clustering results, with strong agreement metrics and minimal information loss, indicating its robustness in capturing essential structural and physicochemical properties. Tanimoto and Hamming distance networks yield valuable clustering outcomes, albeit with moderate performance, while the Levenshtein distance network shows significant discrepancies. The analysis of eigenvector centrality across different networks identifies key inhibitors acting as hubs, which are likely critical in biochemical pathways. Community detection results highlight distinct clustering patterns, with well-defined communities providing insights into the functional and structural groupings of BACE-1 inhibitors. The study also conducts non-parametric tests, revealing significant differences in molecular descriptors, validating the clustering methodology. Despite its limitations, including reliance on specific descriptors and computational complexity, this study offers a comprehensive framework for understanding molecular interactions and guiding therapeutic interventions. Future research could integrate additional descriptors, advanced machine learning techniques, and dynamic network analysis to enhance clustering accuracy and applicability.

Clinical Presentation and Molecular Characterization of 3 Patients with Vici Syndrome: Two Novel Variants in the EPG5 Gene.

Introduction: Vici syndrome is an ultra-rare, congenital disorder of autophagy characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency, developmental delay, and hypopigmentation. Patients usually present in the neonatal period or infancy with profound hypotonia, based on information available from the nearly 100 cases reported to date. Case Presentation: We present 3 new cases of Vici syndrome confirmed by genetic analysis of EPG5 gene. The 3 male patients had neonatal hypotonia, progressive microcephaly, psychomotor retardation, recurrent respiratory tract infections, optic atrophy, and failure to thrive, but no cataracts or hepatomegaly. Three disease-causing variants in homozygous state were detected in the EPG5 gene: two novel c.1652C>T and c.7557+2T>C forms; and one previously reported c.7447C>T. The patient, who was homozygous for the c.1652C>T mutation, presented with neonatal onset seizures that had not been reported previously. Discussion/Conclusion: The present study provides data for the evaluation of the natural history and genotype-phenotype correlations for treatment options that are expected to be available in the future.

Clinical, biochemical, and molecular insights into Cerebrotendinous Xanthomatosis: A nationwide study of 100 Turkish individuals.

OBJECTIVE: Cerebrotendinous xanthomatosis (CTX) is an inherited metabolic disorder characterized by progressive neurologic and extraneurologic findings. The aim of this retrospective, descriptive study was to explore the time of presentation and diagnosis, and to expand the phenotype and genotype of CTX, based on a nationwide and comprehensive series of patients in Turkey. METHODS: The demographic, clinical, biochemical and genotypic characteristics of the CTX patients were reviewed. Data on molecular analysis, age of onset and diagnosis, diagnostic delay, neurologic and extraneurologic symptomatology, results of plasma cholestanol levels, brain magnetic resonance imaging and electromyography at the time of diagnosis were reviewed. RESULTS: 100 confirmed CTX patients from 72 families were included. The mean age at diagnosis was 28.16 ± 14.28 years, and diagnostic delay was 18.39 ± 13.71 years. 36 patients were diagnosed in childhood. Frequency of intention tremor (p = 0.069), peripheral neuropathy (p = 0.234) and psychiatric manifestations (p = 0.396) did not differ between two groups, demonstrating the high rate in pediatric patients. Three adult patients showed a milder phenotype without neurologic involvement. Seven patients had normal plasma cholestanol levels despite neurological impairment. Sequencing of the CYP27A1 gene revealed 25 different variants, with a novel c.671_672del variant not previously described in literature. CONCLUSION: Based on the observations of this Turkish CTX cohort, it is emphasized that the true prevalence of CTX is probably underestimated and that it has a wide spectrum of clinical phenotypes even without neurological impairment. In children, abnormal cerebellar findings, peripheral neuropathy and psychiatric findings associated with intellectual disability have been suggested as warning signs to avoid diagnostic delay. In cases of clinical suspicion, molecular analysis is recommended despite normal plasma cholestanol levels, as severe neurologic involvement may occur in CTX patients without elevated cholestanol levels.

Transcriptome-wide analysis uncovers regulatory elements of the antennal transcriptome repertoire of bumblebee at different life stages.

Bumblebees are crucial pollinators, providing essential ecosystem services and global food production. The success of pollination services relies on the interaction between sensory organs and the environment. The antenna functions as a versatile multi-sensory organ, pivotal in mediating chemosensory/olfactory information, and governs adaptive responses to environmental changes. Despite an increasing number of RNA-sequencing studies on insect antenna, comprehensive antennal transcriptome studies at the different life stages were not elucidated systematically. Here, we quantified the expression profile and dynamics of coding/microRNA genes of larval head and antennal tissues from early- and late-stage pupa to the adult of Bombus terrestris as suitable model organism among pollinators. We further performed Pearson correlation analyses on the gene expression profiles of the antennal transcriptome from larval head tissue to adult stages, exploring both positive and negative expression trends. The positively correlated coding genes were primarily enriched in sensory perception of chemical stimuli, ion transport, transmembrane transport processes and olfactory receptor activity. Negatively correlated genes were mainly enriched in organic substance biosynthesis and regulatory mechanisms underlying larval body patterning and the formation of juvenile antennal structures. As post-transcriptional regulators, miR-1000-5p, miR-13b-3p, miR-263-5p and miR-252-5p showed positive correlations, whereas miR-315-5p, miR-92b-3p, miR-137-3p, miR-11-3p and miR-10-3p exhibited negative correlations in antennal tissue. Notably, based on the inverse expression relationship, positively and negatively correlated microRNA (miRNA)-mRNA target pairs revealed that differentially expressed miRNAs predictively targeted genes involved in antennal development, shaping antennal structures and regulating antenna-specific functions. Our data serve as a foundation for understanding stage-specific antennal transcriptomes and large-scale comparative analysis of transcriptomes in different insects.

Concurrent Cobalamin C and Plasminogen Deficiencies in a Patient with Chronic Thrombotic Microangiopathy.

BACKGROUND: Although most patients with atypical hemolytic uremic syndrome (aHUS) have variants in genes participating in alternative complement pathways, rare variants in non-complement pathway-related genes, including DGKE, INF2, MMACHC, PLG, and THBD, have also been described. CASE PRESENTATION: We report an 18-year-old male patient with renal biopsy-proven chronic thrombotic microangiopathy that raised suspicion of aHUS. Whole-exome sequencing revealed a novel pathogenic homozygous MMACHC c.484G>T (p.Gly162Trp) variant. Subsequently, clinical and laboratory findings confirmed cobalamin C (Cbl C) deficiency. Also, homozygous missense c.1112C>T PLG (p.Thr371Ile) variant was detected (it had been reported as a variant of unknown significance). However, the low serum plasminogen (PLG) activity proved the pathogenicity of c.1112C>T. Hence, the patient was diagnosed with concurrent Cbl C and PLG deficiencies. Segregation analysis revealed that the mother and father had the same heterozygous PLG and MMACHC variants. PLG variants have generally been described in aHUS patients concomitant with complement gene variants in the literature; therefore, the association between aHUS and PLG variants is controversial. The possible contribution of PLG deficiency to thrombotic microangiopathy was also discussed in this case. CONCLUSION: Non-complement-mediated aHUS is an exceptional disorder. A limited number of genes are involved in this entity. To our knowledge, this is the first aHUS patient diagnosed with both Cbl C and PLG deficiencies in the literature.

A different perspective into clinical symptoms in CPT I deficiency.

Carnitine palmitoyltransferase I (CPT I) deficiency is an autosomal recessive disorder causing long-chain fatty acid oxidation defect, characterized by metabolic decompensation episodes accompanied by hypoketotic hypoglycemia, hepatomegaly, seizures, renal tubular acidosis, and hyperammonemia. The aim of this study was to investigate the neurological symptoms in CPT I deficiency and different outcomes with respect to predisposing factors for sequela and to draw attention to the neurological impairment that may develop during the course of the disease. The retrospective study reviewed clinical characteristics of 14 patients. Mean follow-up period was 10.3 ± 4.7 (range: 8 months-18.6 years; median: 10 years) years. Three patients were diagnosed with newborn screening. In the symptomatic group (n = 12) most common presenting symptoms were psychomotor retardation (n = 6), seizures (n = 5), encephalopathy (n = 5), dystonia (n = 1), Reye-like syndrome (n = 5), muscle weakness (n = 3), and autism (n = 1). Neurologic findings detected in the follow-up period included speech disorder (n = 9), abnormal cranial MRI findings (n = 5), neuropathy (n = 1), and attention deficit hyperactivity disorder (n = 1). Speech disorders collectively included delayed expressive language development, speech articulation disorder, speech delay, stuttering, and specific speech difficulties. After starting treatment for CPT I deficiency, speech disorders improved in 3 patients. Our findings confirmed that the clinical manifestations of CPT I deficiency is wider than previously thought, causing specific neurologic dysfunction, mainly speech disorders at a large scale, that were unexpected in a fatty acid oxidation disorder. We suggest that early diagnosis and treatment is the key factor to prevent neurologic sequelae while an extensive neurological evaluation is essential in patients with CPT I deficiency both at the time of diagnosis and during the follow-up period.

Low relapse rate in patients with giant cell arteritis in a multi-centre retrospective Turkish Registry.

OBJECTIVES: Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only protocol arms in controlled trials of tocilizumab and abatacept in 12-24 months. Herein, we aimed to assess the real-life relapse rates retrospectively in patients with GCA from Turkey. METHODS: We assembled a retrospective cohort of patients with GCA diagnosed according to ACR 1990 criteria from tertiary rheumatology centres in Turkey. All clinical data were abstracted from medical records. Relapse was defined as any new manifestation or increased acutephase response leading to the change of the GC dose or use of a new therapeutic agent by the treating physician. RESULTS: The study included 330 (F/M: 196/134) patients with GCA. The mean age at disease onset was 68.9±9 years. The most frequent symptom was headache. Polymyalgia rheumatica was also present in 81 (24.5%) patients. Elevation of acute phase reactants (ESR>50 mm/h or CRP>5 mg/l) was absent in 25 (7.6%) patients at diagnosis. Temporal artery biopsy was available in 241 (73%) patients, and 180 of them had positive histopathological findings for GCA. For remission induction, GC pulses (250-1000 methylprednisolone mg/3-7 days) were given to 69 (20.9%) patients, with further 0.5-1 mg/kg/day prednisolone continued in the whole group. Immunosuppressives as GC-sparing agents were used in 252 (76.4%) patients. During a follow-up of a median 26.5 (6-190) months, relapses occurred in 49 (18.8%) patients. No confounding factor was observed in relapse rates. GC treatment could be stopped in only 62 (23.8%) patients. Additionally, GC-related side effects developed in 64 (24.6%) patients, and 141 (66.2%) had at least one Vasculitis Damage Index (VDI) damage item present during follow-up. CONCLUSIONS: In this first multi-centre series of GCA from Turkey, we observed that only one-fifth of patients had relapses during a mean follow-up of 26 months, with 76.4% given a GC-sparing IS agent at diagnosis. At the end of follow-up, GC-related side effects developed in one-fourth of patients. Our results suggest that patients with GCA had a low relapse rate in real-life experience of a multi-centre retrospective Turkish registry, however with a significant presence of GC-associated side effects during follow-up.

Evaluation of the risk factors for noncommunicable diseases in patients with inborn errors of amino acid metabolism receiving nutrition therapy.

OBJECTIVES: There is growing concern about the low-protein and high-energy diet therapies used in the treatment of inherited amino acid metabolism disorders. We aimed to identify the risk factors for noncommunicable diseases that may arise from nutritional therapies and suggests approaches that may prevent the development of the noncommunicable diseases. METHODS: The present study evaluates 112 patients, on long-term nutritional therapy for at least the last 2 years with a diagnosis of an inborn error of the amino acid metabolism, and their 28 healthy siblings. The participants are assessed for the development of overweight and metabolic syndrome based on an analysis of anthropometric parameters, body composition and the results of biochemical tests. RESULTS: Anthropometric measurements including BMI, weight Z-score, waist circumference and fat mass were not significantly different between patients and controls. Height Z-scores were similar in phenylketonuria patients compared to controls, but lower in urea cycle disorders, organic acidemia and maple syrup urine disease groups. No increased risk of development of overweight or metabolic syndrome was detected in the patient group, while there were findings suggesting malnutrition in patients diagnosed with urea cycle disorders. There was a correlation between patients' BMI and C3-carnitine levels in organic acidemia patients and leucine levels in maple syrup urine disease patients. CONCLUSIONS: All forms of malnutrition can be prevented in patient groups receiving limited nutrients under a dietary management protocol, based on the findings of anthropometric and biochemical evaluations and analyses of body composition.

Paraneoplastic arthritis: a series of 92 cases.

OBJECTIVES: Paraneoplastic arthritis (PA) is one of the paraneoplastic syndromes. Both laboratory and clinical findings similar to rheumatological diseases can be seen. In this study, we aimed to present the clinical and laboratory findings, malignancy type, and pathological diagnoses of patients with paraneoplastic arthritis. METHODS: In a multicentre retrospective study, 92 patients with PA from the last 10 years were included in the study. RESULTS: Patients with PA and hematological malignancies detected the highest ratio of lymphomas (25,6%). The most common cancer detected in patients with solid malignancy and PA was lung cancer (41.5%). All malignant patients with PA had significant Anti-CCP positivity compared with the healthy control group (P= 0.014). CONCLUSION: As a result, although PA is a rare condition, it can be confused with many rheumatological diseases. The most commonly involved joint is the knee joint, followed by the ankle and hand-wrist. Autoantibody negativity, high LDH level, and arthritis unresponsive to treatment constitute important clues for diagnosis.

Novel GALT variations and genetic spectrum in Turkish population with the correlation of genotype and phenotype.

Classic galactosemia (OMIM#230400) is an autosomal recessive inborn error of carbohydrate metabolism caused by a deficiency of the galactose-1-phosphate-uridyl-transferase enzyme encoded by the GALT gene. Even though a galactose-restricted diet efficiently resolves the acute complications, it is insufficient to prevent long-term complications regarding speech defects, intellectual functioning, premature ovarian failure, cataract, hepatomegaly, dysarthria, ataxia, and tremor. Seventy-seven patients who were genetically diagnosed with classic galactosemia were included in this cohort. Identified novel variants were classified based on their predicted effect on the GALT function. Further, potential genotype-phenotype correlations were investigated via statistical analysis. In total, 18 different sequence variants were identified, including four novels (c.200delG/p.(Arg67Profs* 19), c.533T>G/ p.(Met178Arg), c.708_709delGT/p.(Ser236Argfs* 30), c.467C>A/p.(Ser156* )). Jaundice was the most common short-term finding with 80% (61/77). Even with early diagnosis, intellectual disability is encountered with 36% (27/74) of the long-term complications. Patients with biallelic missense variants have a significantly higher prevalence of cataracts (OR: 17.9). Longitudinal observations showed attenuation of cataracts and hepatomegaly. This study has shown the GALT variation spectrum of the Turkish population with a 30-year retrospective cohort, submitting a significant contribution to the genotype/phenotype correlation in galactosemia. This study also highlights the cost-effective importance of Sanger sequencing in the diagnosis of single-gene metabolic diseases.

Levodopa-refractory hyperprolactinemia and pituitary findings in inherited disorders of biogenic amine metabolism.

Elevated serum prolactin concentrations occur in inherited disorders of biogenic amine metabolism because dopamine deficiency leads to insufficient inhibition of prolactin secretion. This work from the International Working Group on Neurotransmitter Related Disorders (iNTD) presents the results of the first standardized study on levodopa-refractory hyperprolactinemia (LRHP; >1000 mU/L) and pituitary magnetic resonance imaging (MRI) abnormalities in patients with inherited disorders of biogenic amine metabolism. Twenty-six individuals had LRHP or abnormal pituitary findings on MRI. Tetrahydrobiopterin deficiencies were the most common diagnoses (n = 22). The median age at diagnosis of LRHP was 16 years (range: 2.5-30, 1st-3rd quartiles: 12.25-17 years). Twelve individuals (nine females) had symptoms attributed to hyperprolactinemia: menstruation-related abnormalities (n = 7), pubertal delay or arrest (n = 5), galactorrhea (n = 3), and decreased sexual functions (n = 2). MRI of the pituitary gland was obtained in 21 individuals; six had heterogeneity/hyperplasia of the gland, five had adenoma, and 10 had normal findings. Eleven individuals were treated with the dopamine agonist cabergoline, ameliorating the hyperprolactinemia-related symptoms in all those assessed. Routine monitoring of these symptoms together with prolactin concentrations, especially after the first decade of life, should be taken into consideration during follow-up evaluations. The potential of slow-release levodopa formulations and low-dose dopamine agonists as part of first-line therapy in the prevention and treatment of hyperprolactinemia should be investigated further in animal studies and human trials. This work adds hyperprolactinemia-related findings to the current knowledge of the phenotypic spectrum of inherited disorders of biogenic amine metabolism.

Clinical and bi-genomic DNA findings of patients suspected to have mitochondrial diseases.

Background: Mitochondrial diseases are the most common group of inherited metabolic disorders, causing difficulties in definite diagnosis due to clinical and genetic heterogeneity. Clinical components are predominantly associated with pathogenic variants shown in nuclear or mitochondrial genomes that affect vital respiratory chain function. The development of high-throughput sequencing technologies has accelerated the elucidation of the genetic etiology of many genetic diseases that previously remained undiagnosed. Methods: Thirty affected patients from 24 unrelated families with clinical, radiological, biochemical, and histopathological evaluations considered for mitochondrial diseases were investigated. DNA isolated from the peripheral blood samples of probands was sequenced for nuclear exome and mitochondrial DNA (mtDNA) analyses. MtDNA sequencing was also performed from the muscle biopsy material in one patient. For segregation, Sanger sequencing is performed for pathogenic alterations in five other affected family members and healthy parents. Results: Exome sequencing revealed 14 different pathogenic variants in nine genes encoding mitochondrial function peptides (AARS2, EARS2, ECHS1, FBXL4, MICOS13, NDUFAF6, OXCT1, POLG, and TK2) in 12 patients from nine families and four variants in genes encoding important for muscle structure (CAPN3, DYSF, and TCAP) in six patients from four families. Three probands carried pathogenic mtDNA variations in two genes (MT-ATP6 and MT-TL1). Nine variants in five genes are reported for the first time with disease association: (AARS2: c.277C>T/p.(R93*), c.845C>G/p.(S282C); EARS2: c.319C>T/p.(R107C), c.1283delC/p.(P428Lfs*); ECHS1: c.161G>A/p.(R54His); c.202G>A/p.(E68Lys); NDUFAF6: c.479delA/p.(N162Ifs*27); and OXCT1: c.1370C>T/p.(T457I), c.1173-139G>T/p.(?). Conclusion: Bi-genomic DNA sequencing clarified genetic etiology in 67% (16/24) of the families. Diagnostic utility by mtDNA sequencing in 13% (3/24) and exome sequencing in 54% (13/24) of the families prioritized searching for nuclear genome pathologies for the first-tier test. Weakness and muscle wasting observed in 17% (4/24) of the families underlined that limb-girdle muscular dystrophy, similar to mitochondrial myopathy, is an essential point for differential diagnosis. The correct diagnosis is crucial for comprehensive genetic counseling of families. Also, it contributes to making treatment-helpful referrals, such as ensuring early access to medication for patients with mutations in the TK2 gene.

Triosephosphate Isomerase Deficiency: E105D Mutation in Unrelated Patients and Review of the Literature.

Introduction: Chronic haemolytic anaemia, increased susceptibility to infections, cardiomyopathy, neurodegeneration, and death in early childhood are the clinical findings of triosephosphate isomerase (TPI) deficiency, which is an ultra-rare disorder. The clinical and laboratory findings and the outcomes of 2 patients with TPI deficiency are reported, with a review of cases reported in the literature. Case Presentation: Two unrelated patients with haemolytic anaemia and neurologic findings who were diagnosed as having TPI deficiency are presented. Neonatal onset of initial symptoms was observed in both patients, and the age at diagnosis was around 2 years. The patients had increased susceptibility to infections and respiratory failure, but cardiac symptoms were not remarkable. Screening for inborn errors of metabolism revealed a previously unreported metabolic alteration determined using tandem mass spectrometry in acylcarnitine analysis, causing elevated propionyl carnitine levels in both patients. The patients had p.E105D (c.315G>C) homozygous mutations in the TPI1 gene. Although severely disabled, both patients are alive at the ages of 7 and 9 years. Discussion: For better management, it is important to investigate the genetic aetiology in patients with haemolytic anaemia with or without neurologic symptoms who do not have a definitive diagnosis. The differential diagnosis of elevated propionyl carnitine levels using tandem mass spectrometry screening should also include TPI deficiency.

Empirical investigation on how wellbeing-related infrastructure shapes economic growth: Evidence from the European Union regions.

One of the most important policies of the European Union is regional development, which comprises measures of enhancing economic growth and citizens' living standards via strategic investment. Considering that economic growth and wellbeing are intertwined from the perspective of EU policies, this study examines the relationship between wellbeing-related infrastructure and economic growth in 212 NUTS 2 regional subdivisions across the members of Eu-28 during the period 2001-2020. We therefore analyzed data from 151 Western Europe regions and 61 Central and Eastern Europe regions by means of a panel data analysis with the first-difference generalized method of moments estimator. Our main interest was to determine the degree to which Western Europe regions responded to predictors as compared to Central and Eastern Europe regions. According to the empirical results, the predictors with the strongest influence for Western Europe regions were disposable household income, inter-regional mobility, housing indicator, labor force and participation. For Central and Eastern Europe regions, the largest impact was triggered by the housing indicator, internet broadband access and air pollution. In addition, we determined a relational weighted multiplex between all variables of interest by using dynamic time warping and we introduced topological measures in a multilayer multiplex model for both regional subsamples.

Discrete Geodesic Distribution-Based Graph Kernel for 3D Point Clouds.

In the structural analysis of discrete geometric data, graph kernels have a great track record of performance. Using graph kernel functions provides two significant advantages. First, a graph kernel is capable of preserving the graph's topological structures by describing graph properties in a high-dimensional space. Second, graph kernels allow the application of machine learning methods to vector data that are rapidly evolving into graphs. In this paper, the unique kernel function for similarity determination procedures of point cloud data structures, which are crucial for several applications, is formulated. This function is determined by the proximity of the geodesic route distributions in graphs reflecting the discrete geometry underlying the point cloud. This research demonstrates the efficiency of this unique kernel for similarity measures and the categorization of point clouds.

Reanalysis of exome sequencing data reveals a treatable neurometabolic origin in two previously undiagnosed siblings with neurodevelopmental disorder.

Neurodevelopmental disorders (NDDs) have broad heterogeneity both clinically and genetically. Inborn errors of metabolism can be one of the reasons of neurodevelopmental disruption causing specific NDDs. Although there is tremendous advance in molecular identification via next-generation sequencing (NGS), there are still many unsolved patients with NDD. Reanalysis of NGS data with different pipelines can at least partially accomplish this challenge. Herein, we report clinic and genetic components of an adult sib-pair with an undiagnosed NDD condition, which has been solved through reanalysis of whole-exome sequencing (WES). Parallel analysis of SNP-based genotyping and WES was performed to focus on variants only in loci with positive logarithm of the odds scores. WES data was analyzed through three different pipelines with two distinct bed files. Reanalysis of WES data led us to detect a homozygous FOLR1 variant (ENST00000393676.5:c.610C > T, p.(Arg204Ter), rs952165627) in the affected sib-pair. Surprisingly, the variant could not be detected in the first analysis as the variant region is not included in the first bed file which may frequently be used. Biochemical tests of CSF have confirmed the genetic analysis, CSF folic acid levels were detected low in sib-pair, and intravenous folinic acid treatment improved the disease course for the first 6 months of follow-up even at late diagnosis age. Although combined analysis of SNP-based genotyping and WES is a powerful tool to reveal the genetic components of heterogeneous diseases, reanalysis of genome data still should be considered in unsolved patients. Also, biochemical screening helps us to decipher undiagnosed NDD that may be a treatable neurometabolic condition.

Assessing Crimp of Fibres in Random Networks with 3D Imaging.

The analysis of fibrous structures using micro-computer tomography (µCT) is becoming more important as it provides an opportunity to characterise the mechanical properties and performance of materials. This study is the first attempt to provide computations of fibre crimp for various random fibrous networks (RFNs) based on µCT data. A parametric algorithm was developed to compute fibre crimp in fibres in a virtual domain. It was successfully tested for six different X-ray µCT models of nonwoven fabrics. Computations showed that nonwoven fabrics with crimped fibres exhibited higher crimp levels than those with non-crimped fibres, as expected. However, with the increased fabric density of the non-crimped nonwovens, fibres tended to be more crimped. Additionally, the projected fibre crimp was computed for all three major 2D planes, and the obtained results were statistically analysed. Initially, the algorithm was tested for a small-size, nonwoven model containing only four fibres. The fraction of nearly straight fibres was computed for both crimped and non-crimped fabrics. The mean value of the fibre crimp demonstrated that fibre segments between intersections were almost straight. However, it was observed that there were no perfectly straight fibres in the analysed RFNs. This study is applicable to approach employing a finite-element analysis (FEA) and computational fluid dynamics (CFD) to model/analyse RFNs.

A Series-Based Deep Learning Approach to Lung Nodule Image Classification.

Although many studies have shown that deep learning approaches yield better results than traditional methods based on manual features, CADs methods still have several limitations. These are due to the diversity in imaging modalities and clinical pathologies. This diversity creates difficulties because of variation and similarities between classes. In this context, the new approach from our study is a hybrid method that performs classifications using both medical image analysis and radial scanning series features. Hence, the areas of interest obtained from images are subjected to a radial scan, with their centers as poles, in order to obtain series. A U-shape convolutional neural network model is then used for the 4D data classification problem. We therefore present a novel approach to the classification of 4D data obtained from lung nodule images. With radial scanning, the eigenvalue of nodule images is captured, and a powerful classification is performed. According to our results, an accuracy of 92.84% was obtained and much more efficient classification scores resulted as compared to recent classifiers.