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Background: Advanced lung diseases are prevalent in women, yet are underrecognized and under-treated due to differing epidemiology and pathophysiology., Aim: To investigate any gender differences in access to palliative care and end-of-life management for patients with advanced lung diseases., Methods: A post-hoc analysis was conducted using three datasets that included information regarding the provision of palliative care to patients with advanced lung diseases - chronic obstructive pulmonary disease (COPD), fibrotic interstitial lung diseases (f-ILD) or non-small cell lung cancer (NSCLC) in tertiary and regional hospitals in Victoria, Australia, from 2004 to 2019., Results: 343 patients with advanced COPD, 67 with f-ILD and 1022 with NSCLC were included. Compared to men, women with COPD (n = 126, 36.7%) were less likely to have smoked ( P = 0.024), had significantly worse lung function ( P < 0.001), and were more likely to receive non-invasive ventilation at end of life ( P = 0.021). Women with fibrotic ILDs (n = 30, 44.8%) had significantly worse lung function ( P < 0.001) and were more likely to experience exacerbations during their last two years of life ( P < 0.001). Women with NSCLC (n = 457, 44.7%) were significantly younger ( P < 0.001), less likely to have smoked ( P < 0.001) or had asbestos exposure ( P < 0.001). There were no significant differences between men and women with advanced lung diseases regarding referral to palliative care services ( P = 0.369), hospital place of death ( P = 0.915), or end-of-life management., Conclusions: Despite differences in lung function, exacerbations and targeted therapies, men and women with advanced lung diseases received equal access to symptom palliation and palliative care services towards the end of life., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: I confirm that this study has been approved (including for publication) by the Melbourne Health Research Ethics Committee, the Austin Health Human Research Ethics Committee and the Peter MacCallum Cancer Centre Human Research Ethics Committee.

The primary objective of this study was to evaluate the association between preweaning diarrhea and measures of survival, health, and production. The measures of interest included survival (mortality before first calving and time to removal from the herd), health (retained fetal membranes, metritis, mastitis, and SCC), and production (305-d mature-equivalent milk yield and time to first calving). A secondary objective was to investigate if these associations varied according to the age of the calf when the case of diarrhea occurred. Herd records from a farm located in Southern Australia were used to conduct a retrospective cohort study where subjects (calves) with diarrhea were enrolled at the time of their first case along with 2 subjects without diarrhea, matched for age (±3 d) and date of birth (±15 d), amounting to 9,833 calves in the dataset. Survival analysis was conducted to determine whether preweaning diarrhea was associated with death in the short term (first 20 d after enrollment), medium term (21-100 d after enrollment) and long term (101 d after enrollment to first calving). Crude incidence rate ratios, Kaplan-Meier curves, and hazard ratios (HR, Cox regression) were derived for each event-based outcome (e.g., death, calving, mastitis). Multivariable linear models were used for continuous outcomes. Calves with preweaning diarrhea had greater mortality rates in the short term (HR = 2.48, 95% CI: 1.87-3.29) and medium term (HR = 1.89, 95% CI: 1.41-2.55), but not in the long term (HR = 0.98, 95% CI: 0.79-1.22). A small negative association between preweaning diarrhea and time to first calving was found, with calves with diarrhea calving 4 d later than calves without diarrhea (HR = 0.95, 95% CI: 0.91-1.00). Rates of postcalving removal from the herd (death or culling) were higher in calves with a history of preweaning diarrhea (HR = 1.13, 95% CI: 1.01 to 1.26), as were peak lactation log SCC (+0.08, 95% CI: 0.02 to 0.14). Further research is needed to replicate these novel findings, as they are based on exploratory analyses and could be spurious findings. No substantial associations were observed for the other measures of interest. Our study findings support existing research demonstrating the importance of preweaning diarrhea as a substantial cause of calf mortality and raise new hypotheses about other potential impacts during lactation., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Lung function testing remains a cornerstone in the assessment and management of interstitial lung disease (ILD) patients. The clinical implications of the Global Lung function Initiative (GLI) reference equations and the updated interpretation strategies remain uncertain., Methods: Adult patients with ILD with baseline forced vital capacity (FVC) were included from the Australasian ILD registry and the National Healthcare Group ILD registry, Singapore.The European Coal and Steel Community and Miller reference equations were compared with the GLI reference equations to assess (a) differences in lung function percent predicted values; (b) ILD risk prediction models and (c) eligibility for ILD clinical trial enrolment., Results: Among 2219 patients with ILD, 1712 (77.2%) were white individuals. Idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD and unclassifiable ILD predominated.Median FVC was 2.60 (2.01-3.36) L, forced expiratory volume in 1 s was 2.09 (1.67-2.66) L and diffusing capacity of the lungs for carbon monoxide (DLCO) was 13.60 (10.16-17.60) mL/min/mm Hg. When applying the GLI reference equations, the mean FVC percentage predicted was 8.8% lower (87.7% vs 78.9%, p<0.01) while the mean DLCO percentage predicted was 4.9% higher (58.5% vs 63.4%, p<0.01). There was a decrease in 19 IPF and 119 non-IPF patients who qualified for the nintedanib clinical trials when the GLI reference equations were applied. Risk prediction models performed similarly in predicting mortality using both reference equations., Conclusion: Applying the GLI reference equations in patients with ILD leads to higher DLCO percentage predicted values and smaller lung volume percentage predicted values. While applying the GLI reference equations did not impact on prognostication, fewer patients met the clinical trial criteria for antifibrotic agents., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Pharmacogenetics currently supports clinical decision-making on the basis of a limited number of variants in a few genes and may benefit paediatric prescribing where there is a need for more precise dosing. Integrating genomic information such as methylation into pharmacogenetic models holds the potential to improve their accuracy and consequently prescribing decisions. Cytochrome P450 2D6 ( CYP2D6 ) is a highly polymorphic gene conventionally associated with the metabolism of commonly used drugs and endogenous substrates. We thus sought to predict epigenetic loci from single nucleotide polymorphisms (SNPs) related to CYP2D6 in children from the GUSTO cohort., Methods: Buffy coat DNA methylation was quantified using the Illumina Infinium Methylation EPIC beadchip. CpG sites associated with CYP2D6 were used as outcome variables in Linear Regression, Elastic Net and XGBoost models. We compared feature selection of SNPs from GWAS mQTLs, GTEx eQTLs and SNPs within 2 MB of the CYP2D6 gene and the impact of adding demographic data. The samples were split into training (75%) sets and test (25%) sets for validation. In Elastic Net model and XGBoost models, optimal hyperparameter search was done using 10-fold cross validation. Root Mean Square Error and R-squared values were obtained to investigate each models' performance. When GWAS was performed to determine SNPs associated with CpG sites, a total of 15 SNPs were identified where several SNPs appeared to influence multiple CpG sites., Results: Overall, Elastic Net models of genetic features appeared to perform marginally better than heritability estimates and substantially better than Linear Regression and XGBoost models. The addition of nongenetic features appeared to improve performance for some but not all feature sets and probes. The best feature set and Machine Learning (ML) approach differed substantially between CpG sites and a number of top variables were identified for each model., Discussion: The development of SNP-based prediction models for CYP2D6 CpG methylation in Singaporean children of varying ethnicities in this study has clinical application. With further validation, they may add to the set of tools available to improve precision medicine and pharmacogenetics-based dosing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fong, Tan, Garg, Teh, Pan, Gupta, Krishna, Chen, Purwanto, Yap, Tan, Chan, Chan, Goh, Rane, Tan, Jiang, Han, Meaney, Wang, Keppo and Tan.)

Introduction: The heterogeneity of depressive and anxiety disorders complicates clinical management as it may account for differences in trajectory and treatment response. Self-schemas, which can be determined by Self-Referential Judgements (SRJs), are heterogeneous yet stable. SRJs have been used to characterize personality in the general population and shown to be prognostic in depressive and anxiety disorders., Methods: In this study, we used SRJs from a Self-Referential Encoding Task (SRET) to identify clusters from a clinical sample of 119 patients recruited from the Institute of Mental Health presenting with depressive or anxiety symptoms and a non-clinical sample of 115 healthy adults. The generated clusters were examined in terms of most endorsed words, cross-sample correspondence, association with depressive symptoms and the Depressive Experiences Questionnaire and diagnostic category., Results: We identify a 5-cluster solution in each sample and a 7-cluster solution in the combined sample. When perturbed, metrics such as optimum cluster number, criterion value, likelihood, DBI and CHI remained stable and cluster centers appeared stable when using BIC or ICL as criteria. Top endorsed words in clusters were meaningful across theoretical frameworks from personality, psychodynamic concepts of relatedness and self-definition, and valence in self-referential processing. The clinical clusters were labeled "Neurotic" (C1), "Extraverted" (C2), "Anxious to please" (C3), "Self-critical" (C4), "Conscientious" (C5). The non-clinical clusters were labeled "Self-confident" (N1), "Low endorsement" (N2), "Non-neurotic" (N3), "Neurotic" (N4), "High endorsement" (N5). The combined clusters were labeled "Self-confident" (NC1), "Externalising" (NC2), "Neurotic" (NC3), "Secure" (NC4), "Low endorsement" (NC5), "High endorsement" (NC6), "Self-critical" (NC7). Cluster differences were observed in endorsement of positive and negative words, latency biases, recall biases, depressive symptoms, frequency of depressive disorders and self-criticism., Discussion: Overall, clusters endorsing more negative words tended to endorse fewer positive words, showed more negative biases in reaction time and negative recall bias, reported more severe depressive symptoms and a higher frequency of depressive disorders and more self-criticism in the clinical population. SRJ-based clustering represents a novel transdiagnostic framework for subgrouping patients with depressive and anxiety symptoms that may support the future translation of the science of self-referential processing, personality and psychodynamic concepts of self-definition to clinical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tan, Wang, Tan, Ong, Ooi, Lee, Rane, Tey, Chua, Goh, Lam, Chakraborty, Yew, Ong, Kee, Lim, Hashim, Lu, Meany, Tolomeo, Lee, Tan and Keppo.)