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Tea leaves’ diseases caused by constant exposure to pathogens lead to significant crop yield loss globally. Diagnosing the tea leave disease at an early stage minimizes the tea yield loss. In this study, a novel approach is presented for automatically detecting tea leaves diseases based on image processing technology. The Non-dominated Sorting Genetic Algorithm (NSGA-II) based image clustering is proposed for detecting the disease area in tea leaves. After that, PCA and multi-class SVM is used for feature reduction and identifying the disease in the tea leaves, respectively. The result shows that the proposed algorithm can detect the type of disease persisting in tea leaves with an average accuracy of 83%. Five different tea leaf diseases are considered here, such as Red Rust, Red Spider, Thrips, Helopeltis, and Sunlight Scorching.

ObjectivesTo determine whether children and young adults with filaggrin (FLG) loss-of-function mutations1 and asthma, with or without eczema, have increased antibiotic use compared to those with wild-type FLG.MethodsWe used the BREATHE dataset, a cross-sectional study (2003–2005) of gene-environment interactions in 1100 children and young adults with physician-diagnosed asthma in Tayside and Fife, Scotland. The prescribing patterns, including annual number of prescriptions for all participants were followed for 14 years (2005–2018).2 Generalised linear mixed models with a negative binomial family and a random effect for the participant were used, adjusted for age, gender and FLG loss-of-function mutations. Genotyping was performed for four FLG loss-of-function mutations, R501X, 2281del4, S3247X and R2447X, the most common in Caucasians. The BREATHE study and subsequent analyses have approval from the Tayside Medical Research and Ethics Committee (reference 2015RC05). Written consent was obtained for all participants.ResultsThe cohort analysed included 1001 participants. 121 had no antibiotic prescription (12.1%), 595 were male (59.4%), and had a mean age of 10.3 years (interquartile range at baseline: 7–13 years old). All participants had an asthma diagnosis, 536 self-reported having eczema (53.5%), and 163 had FLG loss-of-function mutations (16.3%). Total individual antibiotic prescriptions in the study population was 3837. Children and young adults with asthma and eczema carrying FLG mutations had an Incidence Rate Ratio (IRR) of 1.21 (CI 95%: 1.00–1.48) for total antibiotic prescriptions compared to those with wild-type FLG. Children and young adults with asthma and eczema carrying FLG loss-of-function mutations had an IRR of 1.44 (CI 1.00–2.09) for topical antibiotic prescriptions compared to those with wild-type FLG. The IRR estimates were positive for oral antibiotics, first-line urinary tract antibiotics, first-line respiratory antibiotics, and oral macrolides; however, these results were not statistically significant.ConclusionUK children with asthma and eczema carrying FLG loss-of-function mutations have a greater risk of antibiotic use through childhood and early adulthood. This risk is not observed in children with asthma carrying FLG mutations without eczema. The dysfunctional skin barrier present as a primary defect in FLG-deficient individuals,1 potentially worsened by eczema, might act as an underlying factor contributing to increased bacterial entry, reflected in increased antibiotic use throughout childhood. This vulnerable population could benefit from a ersonalized medicine approach where carers are provided tailored information regarding their children’s increased risk for bacterial infections. A limitation is that our study is underpowered as annual prescriptions were low from the relatively large study population.ReferencesPalmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, et al. Nature Genetics. 2006;38(4):441–6.Soares P, Fidler K, Felton J, Tavendale R, Hovels A, Bremner SA, et al. British Journal of Dermatology. 2018;179(3):717–23.

ObjectivesThere is increasing evidence to support the use of personalised medicine-led prescribing in young people’s asthma. However, there is limited knowledge on the views of young people with respect to the motivation and acceptability for genotype directed therapy.MethodsYoung people aged 12–18 years old participating in the PACT pragmatic randomised controlled trial assessing asthma prescribing according to Arg16Gly β2 adrenoceptor genotype1 completed online questionnaires exploring their views on personalised medicine.Results241 online questionnaires were distributed to adolescents who participated in the PACT trial and 186 questionnaires were returned (response rate 77.2%). The majority were happy to be approached to participate in this trial (n = 185, 99.4%). There was almost unanimous agreement that asthma control improved over the course of the study irrespective of the trial arm (n = 185, 99.4%). The majority believed that asthma research would help doctors understand and treat asthma better (n = 181, 97.3%). A small minority had concerns about the use and storage of their DNA for research (n = 12, 6.4%). 36 participants (19.4%) had concerns about having to stop or change their asthma medication.The most important motivating factor was attributed to believing the study would benefit other patients in future (n = 97, 52.2%), followed by curiosity regarding their genetic type and best treatment for asthma (n = 32, 17.2%). Very few had key motivating factors of receiving better care by taking part (n = 1, 0.5%), for closer monitoring (n= 2, 1.1%) or because they thought their asthma would get worse unless they took part (n = 1, 0.5%).ConclusionAdolescents find personalised medicine based asthma treatment trials to be largely acceptable without major concerns regarding the use and storage of DNA for research. The key motivating factor was altruism. The majority felt their asthma improved, which may be attributed to the trial effect. It would be beneficial to investigate parental views and views of communities from different geographical locations, and ethnic and socioeconomic groups.ReferenceRuffles, et al. Asthma prescribing according to Arg16Gly beta-2 genotype: a randomised trial in adolescents, European Respiratory Journal, 2021.

Why did you do this work?Atopic dermatitis (AD), asthma, food allergy and allergic rhinitis are conditions with a significant disease burden in childhood.1 Their aetiology, however, is poorly understood.2 3 The skin-barrier hypothesis is well-understood, in which the skin acts as a barrier to provide protection from external physical and chemical insults and from allergens.4 A defective skin barrier can cause sensitization and subsequent development of one or more allergy-related conditions.5 We therefore sought to investigate the role of genes associated with skin barrier dysfunction on childhood allergy.What did you do?We conducted a systematic review and meta-analysis of the effects of variation in skin-barrier-related genes on childhood allergy-related conditions (registered on PROSPERO; CRD42022355771). A systematic search strategy was used to interrogate Embase, MEDLINE, Emcare, CINAHL and CENTRAL databases, yielding 6018 abstracts. Following abstract screening, 941 full texts were screened using predefined inclusion and exclusion criteria [table 1]. Only reports on genes related to skin-barrier function, identified by the GeneOntology Skin Barrier database,6 were included. Sixty full texts fulfilled the above criteria and were included in the systematic review. Quality assessment was performed for all included full texts, utilizing the validated Quality of Genetic Studies (Q-GENIE) tool.7 Data extraction was performed and data was grouped according to study type and allergic condition. All processes described were conducted by two independent reviewers.What did you find?All included papers (n=60) related to the filaggrin gene (FLG). Meta-analysis was performed on results from 28 papers using Stata-BE statistical software. Remaining papers (n= 32) were assessed by narrative synthesis. We explored associations between FLG variation and atopic dermatitis in cohort [OR 2.43, 95%CI 1.89–3.10; n=13] and case-control [OR 4.44, 95%CI 2.42 – 8.12; n=7] studies. FLG variation was also associated with asthma in cohort studies [OR 1.90, 95%CI 1.33 – 2.7; n=7] and overall allergy in cohort studies [OR 3.01, 95%CI 1.24–7.35; n=3]. In cohort studies which investigated food and non-food allergy separately, FLG variation was associated with food allergy [OR 1.79, 95%CI 1.11 – 2.88; n=4], but not with allergy to non-food substances [OR 1.53, 95%CI 0.85 – 2.73; n=4].What does it mean?Our research emphasises the importance of FLG variation in childhood atopic dermatitis, asthma and allergy. We did not identify clinical evidence indicating roles for other skin barrier-related gene variation in childhood allergy. Limitations of this review include the exclusion of studies not published in the English language and unintentional exclusion of genes not recognised by the GeneOntology Skin Barrier database. In future, there may be a role for exploration of FLG-tailored strategies, aiming to reduce the impact of environmental exposures.Abstract 7784 Table 1Systematic review and meta-analysis inclusion and exclusion criteriaReferencesPunekar YS, Sheikh A. Clinical and experimental allergy. 2009.Tsuge M, Ikeda M, Matsumoto N, Yorifuji T, Tsukahara H. Children. 2021.Yang L, Fu J, Zhou Y. Frontiers in Immunology 2020.Elias P. Current Allergy and Asthma Reports, 2008Egawa GG, Kabashima K. Journal of Allergy and Clinical Immunology 2016.GO:0061436 – Establishment of Skin Barrier, Gene Ontology, 2023Sohani ZN, Meyre D, de Souza RJ, Joseph PG, Gandhi M, Dennis BB, et al. BMC Genetics, 2015

The masses and radii of non-rotating and rotating configurations of pure hadronic stars mixed with self-interacting fermionic asymmetric dark matter are calculated within the two-fluid formalism of stellar structure equations in general relativity. The Equation of State (EoS) of nuclear matter is obtained from the density dependent M3Y effective nucleon–nucleon interaction. We consider the dark matter particle mass of 1 GeV. The EoS of self-interacting dark matter is taken from two-body repulsive interactions of the scale of strong interactions. We explore the conditions of equal and different rotational frequencies of nuclear matter and dark matter and find that the maximum mass of differentially rotating stars with self-interacting dark matter to be ∼ 1.94 M ⊙ with radius ∼ 10.4 km.

Leukotrienes play a central pathophysiological role in both paediatric and adult asthma. However, 35% to 78% of asthmatics do not respond to leukotriene inhibitors. In this study we tested the role of the LTA4H regulatory variant rs2660845 and age of asthma onset in response to montelukast in ethnically diverse populations. We identified and genotyped 3,594 asthma patients treated with montelukast (2,514 late-onset and 1,080 early-onset) from seven cohorts (UKBiobank, GoSHARE, BREATHE, Tayside RCT, PAGES, GALA II and SAGE). Individuals under montelukast treatment experiencing at least one exacerbation in a 12-month period were compared against individuals with no exacerbation, using logistic regression for each cohort and meta-analysis. While no significant association was found with European late-onset subjects, a meta-analysis of 523 early-onset individuals from European ancestry demonstrated the odds of experiencing asthma exacerbations by carriers of at least one G allele, despite montelukast treatment, were increased (odds-ratio = 2.92, 95%confidence interval (CI): 1.04–8.18, I2 = 62%, p = 0.0412) compared to those in the AA group. When meta-analysing with other ethnic groups, no significant increased risk of asthma exacerbations was found (OR = 1.60, 95% CI: 0.61–4.19, I2 = 85%, p = 0.342). Our study demonstrates that genetic variation in LTA4H , together with timing of asthma onset, may contribute to variability in montelukast response. European individuals with early-onset (≤18y) carrying at least one copy of rs2660845 have increased odd of exacerbation under montelukast treatment, presumably due to the up-regulation of LTA4H activity. These findings support a precision medicine approach for the treatment of asthma with montelukast.

Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema. We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379), FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27-4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79-32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24-1.01, p = 0.05), but not related to FLG genotype. In Manchester (n = 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13-3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35-10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16-2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation. We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life.

(1) Background. The endocannabinoid (eCB) system, which regulates physiological and cognitive processes, presents a promising therapeutic target for treating HIV-associated neurocognitive disorders (HAND). Here we examine whether upregulating eCB tone has potential protective effects against HIV-1 Tat (a key HIV transactivator of transcription) protein-induced alterations in synaptic activity. (2) Methods. Whole-cell patch-clamp recordings were performed to assess inhibitory GABAergic neurotransmission in prefrontal cortex slices of Tat transgenic male and female mice, in the presence and absence of the fatty acid amide hydrolase (FAAH) enzyme inhibitor PF3845. Western blot and mass spectrometry analyses assessed alterations of cannabinoid receptor and enzyme protein expression as well as endogenous ligands, respectively, to determine the impact of Tat exposure on the eCB system. (3) Results. GABAergic activity was significantly altered upon Tat exposure based on sex, whereas the effectiveness of PF3845 to suppress GABAergic activity in Tat transgenic mice was not altered by Tat or sex and involved CB1R-related mechanisms that depended on calcium signaling. Additionally, our data indicated sex-dependent changes for AEA and related non-eCB lipids based on Tat induction. (4) Conclusion. Results highlight sex- and/or Tat-dependent alterations of GABAergic activity and eCB signaling in the prefrontal cortex of Tat transgenic mice and further increase our understanding about the role of FAAH inhibition in neuroHIV.

In the era of combined antiretroviral therapy, HIV-1 infected individuals are living longer lives; however, longevity is met with an increasing number of HIV-1 associated neurocognitive disorders (HAND) diagnoses. The transactivator of transcription (Tat) is known to mediate the neurotoxic effects in HAND by acting directly on neurons and also indirectly via its actions on glia. The Go/No-Go (GNG) task was used to examine HAND in the Tat transgenic mouse model. The GNG task involves subjects discriminating between two stimuli sets in order to determine whether or not to inhibit a previously trained response. Data reveal inhibitory control deficits in female Tat(+) mice ( p  = .048) and an upregulation of cannabinoid type 1 receptors (CB 1 R) in the infralimbic (IL) cortex in the same female Tat(+) group ( p  < .05). A significant negative correlation was noted between inhibitory control and IL CB 1 R expression ( r  = −.543, p  = .045), with CB 1 R expression predicting 30% of the variance of inhibitory control ( R 2  = .295, p  = .045). Furthermore, there was a significant increase in spontaneous excitatory postsynaptic current (sEPSC) frequencies in Tat(+) compared to Tat(−) mice ( p  = .008, across sexes). The increase in sEPSC frequency was significantly attenuated by bath application of PF3845, a fatty acid amide hydrolase (FAAH) enzyme inhibitor ( p  < .001). Overall, the GNG task is a viable measure to assess inhibitory control deficits in Tat transgenic mice and results suggest a potential therapeutic treatment for the observed deficits with drugs which modulate endocannabinoid enzyme activity. Graphical Abstract Results of the Go/No-Go operant conditioning task reveal inhibitory control deficits in female transgenic Tat(+) mice without significantly affecting males. The demonstrated inhibitory control deficits appear to be associated with an upregulation of cannabinoid type 1 receptors (CB 1 R) in the infralimbic (IL) cortex in the same female Tat(+) group.

BackgroundAlthough an increased concentration of degraded elastin products in patients with chronic obstructive pulmonary disease (COPD) has been reported for many years, its clinical validity and utility remain uncertain due to technical difficulties, small study groups and the unknown relationship between exacerbation and elastin degradation. The objectives of this study were to determine the validity of urinary and blood total desmosine/isodesmosine in patients with COPD and asthma and to evaluate their relationship to exacerbation status and lung function.MethodsUrinary and blood desmosine levels were measured using validated isotopic dilution liquid chromatography–tandem mass spectrometry methods.Results390 study participants were recruited from the following groups: healthy volunteers, stable asthma, stable and ‘during an exacerbation’ COPD. Compared with healthy non-smokers, we found increased urinary or blood desmosine levels in patients with COPD, but no differences in patients with asthma or healthy smokers. The elevation of urinary desmosine levels was associated with the exacerbation status in patients with COPD. Approximately 40% of patients with stable and ‘during an exacerbation’ COPD showed elevated blood desmosine levels. Blood desmosine levels were strongly associated with age and were negatively correlated with lung diffusing capacity for carbon monoxide.ConclusionThe results suggest that urinary desmosine levels are raised by exacerbations of COPD whereas blood desmosine levels are elevated in a subgroup of patients with stable COPD and reduced lung diffusing capacity. The authors speculate that a raised blood desmosine level may identify patients with increased elastin degradation suitable for targeted therapy. Future prospective studies are required to investigate this hypothesis.