Awareness of alternative gluten-free grains for individuals with coealiac disease

Purpose: Coeliac disease (CD) is a prevalent autoimmune disorder, affecting 1 in 100 of all 4 individuals in the UK. Currently, the only treatment for CD is complete avoidance of gluten, a protein commonly found in wheat, rye and barley. The use of alternative grains (AG) is 6 highly recommended to individuals with CD to improve and diversify their diet. This study aims to determine the current knowledge of the gluten free diet (GFD), consumption rates of AG and awareness of AG, for individuals diagnosed with CD. Methodology: A total of 100 participants were recruited via local coeliac support groups as well as an ‘Allergy and Free From Show’, to participate in a survey. Consent was obtained from all organisations and all individual participants, prior to collecting data. The questionnaire consists of 10 questions, related to participants’ demographic characteristics, 1knowledge of gluten free food (GFF) and AG and consumption rate of AG. Chi-Square (x2) analyses were conducted to compare the variables between gender and time of diagnosis. Findings: Overall, both genders possessed good knowledge of the GFD. Yogurt, vinegar and oats resulted in the highest incorrect responses. It was found that females possesed better knowledge of both GFF and AG. Rice, quinoa and corn were amongst the most popular AG consumed whilst Job’s tears, fonio and sorghum were the least consumed grains. Females reported a higher consumption rate of AG than males. Additionally, those more recently diagnosed had poorer knowledge of the GFD, reduced consumption rates of AG and poor awareness of AG. Originality: It can be suggested that the incorporation of AG into the diet, can prove beneficial for coeliacs and that both knowledge and education, play a fundamental role in determining consumption rates amongst individuals

Food selection behaviour of university students with food allergies and celiac disease

Purpose – Food allergies (FA) and celiac disease (CD) are becoming increasingly prevalent among Late Adolescents (LA) (18–24 years). This period is a challenging developmental stage, whereby individuals transition from parental supervision to the self-management of their FA and CD. Hence, poor food selection behaviour (FSB) is common among these individuals. This study attempted to understand which factors influenced FSB in first-year university students with FA and CD. Design/methodology/approach – A food selection survey was conducted among participants with FA and CD to determine how influential five factors (cost, taste, convenience, health and labelling) were. Descriptive statistics were conducted for the demographic results. The Mann–Whitney U test determined which factors were the most influential, along with sex differences. A comparison was made between FA and CD. Findings – Taste and cost were the most influential determinants of food selection in both groups of participants. Labelling was the least influential factor. Significant differences were found between the sexes. Females were more likely to be influenced by cost, whereas for males, taste was a greater determinant of food choice. Originality/value – This is the first study to explore FSB in late adolescents with FA and CD. The present study confirms previous findings in relation to the FSB of late adolescents. This study contributes evidence suggesting that individuals with and without FA and CD, are influenced by the same determinants of food selection

Adaptive Deep Learning Detection Model for Multi-Foggy Images

The fog has different features and effects within every single environment. Detection whether there is fog in the image is considered a challenge and giving the type of fog has a substantial enlightening effect on image defogging. Foggy scenes have different types such as scenes based on fog density level and scenes based on fog type. Machine learning techniques have a significant contribution to the detection of foggy scenes. However, most of the existing detection models are based on traditional machine learning models, and only a few studies have adopted deep learning models. Furthermore, most of the existing machines learning detection models are based on fog density-level scenes. However, to the best of our knowledge, there is no such detection model based on multi-fog type scenes have presented yet. Therefore, the main goal of our study is to propose an adaptive deep learning model for the detection of multi-fog types of images. Moreover, due to the lack of a publicly available dataset for inhomogeneous, homogenous, dark, and sky foggy scenes, a dataset for multi-fog scenes is presented in this study (https://github.com/Karrar-H-Abdulkareem/Multi-Fog-Dataset). Experiments were conducted in three stages. First, the data collection phase is based on eight resources to obtain the multi-fog scene dataset. Second, a classification experiment is conducted based on the ResNet-50 deep learning model to obtain detection results. Third, evaluation phase where the performance of the ResNet-50 detection model has been compared against three different models. Experimental results show that the proposed model has presented a stable classification performance for different foggy images with a 96% score for each of Classification Accuracy Rate (CAR), Recall, Precision, F1-Score which has specific theoretical and practical significance. Our proposed model is suitable as a pre-processing step and might be considered in different real-time applications

Impact of newborn screening for SCID on the management of congenital athymia

BACKGROUND: Newborn screening (NBS) programmes for severe combined immunodeficiency (SCID) facilitate early SCID diagnosis and promote early treatment with haematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS due to severe T-cell lymphopaenia. With the expanding introduction of NBS programmes, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH), London, United Kingdom. OBJECTIVE: We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH. METHODS: We compared the age at referral and complications between athymic infants diagnosed after clinical presentation (N=25) and patients identified through NBS (N=19), referred for thymus transplantation at GOSH between 10/2019 and 02/2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. RESULTS: Infants referred after NBS identification were significantly younger and had less complications, in particular less infections. All deaths occurred in the non-NBS group, including six patients before and two after thymus transplantation because of pre-existing infections. In the absence of significant co-morbidities or diagnostic uncertainties, timely treatment was more frequently achieved after NBS. Treatment at <4 months of age was associated with higher thymic output at 6- and 12-months post-transplantation. CONCLUSION: NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation prior to acquiring infections or other complications, and facilitating treatment at younger age, thus playing an important role in improving their outcomes

Impact of newborn screening for SCID on the management of congenital athymia

Background Newborn screening (NBS) programs for severe combined immunodeficiency facilitate early diagnosis of severe combined immunodeficiency and promote early treatment with hematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS because of severe T-cell lymphopenia. With the expanding introduction of NBS programs, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH) (London, United Kingdom). Objective We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH. Methods We compared age at referral and complications between athymic infants diagnosed after clinical presentation (n = 25) and infants identified through NBS (n = 19) who were referred for thymus transplantation at GOSH between October 2019 and February 2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. Results The infants referred after identification through NBS were significantly younger and had fewer complications, in particular fewer infections. All deaths occurred in the group of those who did not undergo NBS, including 6 patients before and 2 after thymus transplantation because of preexisting infections. In the absence of significant comorbidities or diagnostic uncertainties, timely treatment was achieved more frequently after NBS. Treatment when younger than age 4 months was associated with higher thymic output at 6 and 12 months after transplantation. Conclusion NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation before they acquire infections or other complications and facilitating treatment at a younger age, thus playing an important role in improving their outcomes

Proteomic-based stratification of intermediate-risk prostate cancer patients

Gleason grading is an important prognostic indicator for prostate adenocarcinoma and is crucial for patient treatment decisions. However, intermediate-risk patients diagnosed in the Gleason grade group (GG) 2 and GG3 can harbour either aggressive or non-aggressive disease, resulting in under- or overtreatment of a significant number of patients. Here, we performed proteomic, differential expression, machine learning, and survival analyses for 1,348 matched tumour and benign sample runs from 278 patients. Three proteins (F5, TMEM126B, and EARS2) were identified as candidate biomarkers in patients with biochemical recurrence. Multivariate Cox regression yielded 18 proteins, from which a risk score was constructed to dichotomize prostate cancer patients into low- and high-risk groups. This 18-protein signature is prognostic for the risk of biochemical recurrence and completely independent of the intermediate GG. Our results suggest that markers generated by computational proteomic profiling have the potential for clinical applications including integration into prostate cancer management

Identification of two novel autism genes, TRPC4 and SCFD2, in Qatar simplex families through exome sequencing

This study investigated the genetic underpinnings of autism spectrum disorder (ASD) in a Middle Eastern cohort in Qatar using exome sequencing. The study identified six candidate autism genes in independent simplex families, including both four known and two novel autosomal dominant and autosomal recessive genes associated with ASD. The variants consisted primarily of de novo and homozygous missense and splice variants. Multiple individuals displayed more than one candidate variant, suggesting the potential involvement of digenic or oligogenic models. These variants were absent in the Genome Aggregation Database (gnomAD) and exhibited extremely low frequencies in the local control population dataset. Two novel autism genes, TRPC4 and SCFD2, were discovered in two Qatari autism individuals. Furthermore, the D651A substitution in CLCN3 and the splice acceptor variant in DHX30 were identified as likely deleterious mutations. Protein modeling was utilized to evaluate the potential impact of three missense variants in DEAF1, CLCN3, and SCFD2 on their respective structures and functions, which strongly supported the pathogenic natures of these variants. The presence of multiple de novo mutations across trios underscored the significant contribution of de novo mutations to the genetic etiology of ASD. Functional assays and further investigations are necessary to confirm the pathogenicity of the identified genes and determine their significance in ASD. Overall, this study sheds light on the genetic factors underlying ASD in Qatar and highlights the importance of considering diverse populations in ASD research

Cloning and functional complementation of ten <i>Schistosoma mansoni</i> phosphodiesterases expressed in the mammalian host stages

Only a single drug against schistosomiasis is currently available and new drug development is urgently required but very few drug targets have been validated and characterised. However, regulatory systems including cyclic nucleotide metabolism are emerging as primary candidates for drug discovery. Here, we report the cloning of ten cyclic nucleotide phosphodiesterase (PDE) genes of S. mansoni, out of a total of 11 identified in its genome. We classify these PDEs by homology to human PDEs. Male worms displayed higher expression levels for all PDEs, in mature and juvenile worms, and schistosomula. Several functional complementation approaches were used to characterise these genes. We constructed a Trypanosoma brucei cell line in which expression of a cAMP-degrading PDE complements the deletion of TbrPDEB1/B2. Inhibitor screens of these cells expressing only either SmPDE4A, TbrPDEB1 or TbrPDEB2, identified highly potent inhibitors of the S. mansoni enzyme that elevated the cellular cAMP concentration. We further expressed most of the cloned SmPDEs in two pde1Δ/pde2Δ strains of Saccharomyces cerevisiae and some also in a specialised strain of Schizosacharomyces pombe. Five PDEs, SmPDE1, SmPDE4A, SmPDE8, SmPDE9A and SmPDE11 successfully complemented the S. cerevisiae strains, and SmPDE7var also complemented to a lesser degree, in liquid culture. SmPDE4A, SmPDE8 and SmPDE11 were further assessed in S. pombe for hydrolysis of cAMP and cGMP; SmPDE11 displayed considerable preferrence for cGMP over cAMP. These results and tools enable the pursuit of a rigorous drug discovery program based on inhibitors of S. mansoni PDEs

A population study of clinically actionable genetic variation affecting drug response from the Middle East

Clinical implementation of pharmacogenomics will help in personalizing drug prescriptions and alleviate the personal and financial burden due to inefficacy and adverse reactions to drugs. However, such implementation is lagging in many parts of the world, including the Middle East, mainly due to the lack of data on the distribution of actionable pharmacogenomic variation in these ethnicities. We analyzed 6,045 whole genomes from the Qatari population for the distribution of allele frequencies of 2,629 variants in 1,026 genes known to affect 559 drugs or classes of drugs. We also performed a focused analysis of genotypes or diplotypes of 15 genes affecting 46 drugs, which have guidelines for clinical implementation and predicted their phenotypic impact. The allele frequencies of 1,320 variants in 703 genes affecting 299 drugs or class of drugs were significantly different between the Qatari population and other world populations. On average, Qataris carry 3.6 actionable genotypes/diplotypes, affecting 13 drugs with guidelines for clinical implementation, and 99.5% of the individuals had at least one clinically actionable genotype/diplotype. Increased risk of simvastatin-induced myopathy could be predicted in ~32% of Qataris from the diplotypes of SLCO1B1, which is higher compared to many other populations, while fewer Qataris may need tacrolimus dosage adjustments for achieving immunosuppression based on the CYP3A5 diplotypes compared to other world populations. Distinct distribution of actionable pharmacogenomic variation was also observed among the Qatari subpopulations. Our comprehensive study of the distribution of actionable genetic variation affecting drugs in a Middle Eastern population has potential implications for preemptive pharmacogenomic implementation in the region and beyond

Impact of newborn screening for SCID on the management of congenital athymia

Background: Newborn screening (NBS) programs for severe combined immunodeficiency facilitate early diagnosis of severe combined immunodeficiency and promote early treatment with hematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS because of severe T-cell lymphopenia. With the expanding introduction of NBS programs, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH) (London, United Kingdom). Objective: We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH. Methods: We compared age at referral and complications between athymic infants diagnosed after clinical presentation (n = 25) and infants identified through NBS (n = 19) who were referred for thymus transplantation at GOSH between October 2019 and February 2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. Results: The infants referred after identification through NBS were significantly younger and had fewer complications, in particular fewer infections. All deaths occurred in the group of those who did not undergo NBS, including 6 patients before and 2 after thymus transplantation because of preexisting infections. In the absence of significant comorbidities or diagnostic uncertainties, timely treatment was achieved more frequently after NBS. Treatment when younger than age 4 months was associated with higher thymic output at 6 and 12 months after transplantation. Conclusion: NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation before they acquire infections or other complications and facilitating treatment at a younger age, thus playing an important role in improving their outcomes