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Background: Over the past two decades, the development of internet-based treatments for adolescents with anxiety and depressive disorders has advanced rapidly. To date, adolescents' preferences and perceived barriers for internet-based treatment remain largely unknown, especially in clinical samples. Therefore, this study explored the preferences and perceived barriers of adolescents with anxiety or depression regarding internet-based treatment., Methods: This qualitative study included 21 adolescent patients with anxiety or depressive disorder, and varied levels of experience with internet-based treatment. Two focus groups (N 1  = 5, N 2  = 6) and semi-structured interviews ( N  = 10) were conducted, recorded, transcribed, and analyzed using a reflexive thematic analysis approach., Results: The thematic analysis yielded five main themes, and 12 subthemes. The main themes were: independence, accessibility, content, therapist contact, and appearance. Adolescents highlighted self-direction as a benefit of internet-based treatment, and motivational challenges as a drawback. They found internet-based interventions convenient and particularly fitting for implementation during waiting periods before formal treatment. Guided interventions were preferred over mere self-help. Furthermore, adolescents stressed the importance of a clear, organized design, and recommended accessibility on both mobile phones and computers., Conclusion: Findings provide a clear overview of the needs and preferences of adolescents with anxiety or depressive disorder regarding internet-based treatment. To address their diverse needs, internet-based interventions should be tailorable, should incorporate therapist guidance, and should already be available during the treatment waiting period. Results of this study can guide the development and implementation of new internet-based interventions, and may thereby help to further optimize their uptake among adolescent patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

In idiopathic pulmonary fibrosis (IPF) constant epithelial micro-injury and aberrant interactions within the stromal micro-environment lead to abnormal alveolar repair and fibrosis. We hypothesized that alveolar epithelial regenerative responses in IPF are impaired due to disturbed crosstalk between epithelial cells and their stromal niche. We established organoid cultures from unfractionated suspensions and isolated EpCAM + cells from distal lung tissue of patients with and without IPF. We observed significantly more organoids being formed from unfractionated suspensions compared to isolated EpCAM + cell cultures, indicating the presence of supportive cells in the unfractionated suspensions. Importantly, lower organoid numbers were observed in unfractionated cultures from IPF lungs compared to non-IPF lungs. This difference was not found when comparing organoid formation from isolated EpCAM + cells alone between IPF and non-IPF groups, suggesting that crosstalk between the supportive population and epithelial cells is impaired in lungs from IPF patients. Additionally, organoids grown from IPF lung-derived cells were larger in size compared to those from non-IPF lungs in both unfractionated and EpCAM + cultures, indicating an intrinsic abnormality in epithelial progenitors from IPF lungs. Together, our observations suggest that dysregulated crosstalk between alveolar progenitor cells and the stromal niche affects the regenerative capacity, potentially contributing to alveolar impairment in IPF., 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 Wisman, Nizamoglu, Noordhoek, Timens, Burgess and Heijink.)

Rationale: Severe asthma and chronic obstructive pulmonary disease (COPD) share common pathophysiological traits such as relative corticosteroid insensitivity. We recently published three transcriptome-associated clusters (TACs) using hierarchical analysis of the sputum transcriptome in asthmatics from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort comprising one Th2-high inflammatory signature (TAC1) and two Th2-low signatures (TAC2 and TAC3)., Objective: We examined whether gene expression signatures obtained in asthma can be used to identify the subgroup of patients with COPD with steroid sensitivity., Methods: Using gene set variation analysis, we examined the distribution and enrichment scores (ES) of the 3 TACs in the transcriptome of bronchial biopsies from 46 patients who participated in the Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease COPD study that received 30 months of treatment with inhaled corticosteroids (ICS) with and without an added long-acting β-agonist (LABA). The identified signatures were then associated with longitudinal clinical variables after treatment. Differential gene expression and cellular convolution were used to define key regulated genes and cell types., Measurements and Main Results: Bronchial biopsies in patients with COPD at baseline showed a wide range of expression of the 3 TAC signatures. After ICS±LABA treatment, the ES of TAC1 was significantly reduced at 30 months, but those of TAC2 and TAC3 were unaffected. A corticosteroid-sensitive TAC1 signature was developed from the TAC1 ICS-responsive genes. This signature consisted of mast cell-specific genes identified by single-cell RNA-sequencing and positively correlated with bronchial biopsy mast cell numbers following ICS±LABA. Baseline levels of gene transcription correlated with the change in RV/TLC %predicted following 30-month ICS±LABA., Conclusion: Sputum-derived transcriptomic signatures from an asthma cohort can be recapitulated in bronchial biopsies of patients with COPD and identified a signature of airway mast cells as a predictor of corticosteroid responsiveness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

COPD is characterized by irreversible lung tissue damage. We hypothesized that lung-derived mesenchymal stromal cells (LMSCs) reduce alveolar epithelial damage via paracrine processes, and may thus be suitable for cell-based strategies in COPD. We aimed to assess whether COPD-derived LMSCs display abnormalities. LMSCs were isolated from lung tissue of severe COPD patients and non-COPD controls. Effects of LMSC conditioned-medium (CM) on H 2 O 2 -induced, electric field- and scratch-injury were studied in A549 and NCI-H441 epithelial cells. In organoid models, LMSCs were co-cultured with NCI-H441 or primary lung cells. Organoid number, size and expression of alveolar type II markers were assessed. Pre-treatment with LMSC-CM significantly attenuated oxidative stress-induced necrosis and accelerated wound repair in A549. Co-culture with LMSCs supported organoid formation in NCI-H441 and primary epithelial cells, resulting in significantly larger organoids with lower type II-marker positivity in the presence of COPD-derived versus control LMSCs. Similar abnormalities developed in organoids from COPD compared to control-derived lung cells, with significantly larger organoids. Collectively, this indicates that LMSCs' secretome attenuates alveolar epithelial injury and supports epithelial repair. Additionally, LMSCs promote generation of alveolar organoids, with abnormalities in the supportive effects of COPD-derived LMCS, reflective of impaired regenerative responses of COPD distal lung cells.

Mesenchymal stromal cells (MSCs) may provide crucial support in the regeneration of destructed alveolar tissue (emphysema) in chronic obstructive pulmonary disease (COPD). We hypothesized that lung-derived MSCs (LMSCs) from patients with emphysema are hampered in their repair capacity, either intrinsically or due to their interaction with the damaged microenvironment. LMSCs were isolated from the lung tissue of controls and patients with severe emphysema and characterized at baseline. In addition, LMSCs were seeded onto control and emphysematous decellularized lung tissue scaffolds and assessed for deposition of extracellular matrix (ECM). We observed no differences in surface markers, differentiation/proliferation potential, and expression of ECM genes between control- and COPD-derived LMSCs. Notably, COPD-derived LMSCs displayed lower expression of FGF10 and HGF messenger RNA (mRNA) and hepatocyte growth factor (HGF) and decorin protein. When seeded on control decellularized lung tissue scaffolds, control- and COPD-derived LMSCs showed no differences in engraftment, proliferation, or survival within 2  wk, with similar ability to deposit new matrix on the scaffolds. Moreover, LMSC numbers and the ability to deposit new matrix were not compromised on emphysematous scaffolds. Collectively, our data show that LMSCs from patients with COPD compared with controls show less expression of FGF10 mRNA, HGF mRNA and protein, and decorin protein, whereas other features including the mRNA expression of various ECM molecules are unaffected. Furthermore, COPD-derived LMSCs are capable of engraftment, proliferation, and functioning on native lung tissue scaffolds. The damaged, emphysematous microenvironment as such does not hamper the potential of LMSCs. Thus, specific intrinsic deficiencies in growth factor production by diseased LMSCs may contribute to impaired alveolar repair in emphysema.

This qualitative case study explores one American Indian (AI) woman's experience of intimate partner violence and the subsequent murder of her abusive partner. The lens of complex personhood (Gordon, 1997) has been applied as a method for understanding "Annie's" multiple identities of AI woman, victim of intimate partner violence, mother, and convicted felon. The aim of the current case study was to uncover implicit and explicit meanings embedded in the experiences of moving from a victim of IPV to an off ender by applying a framework of hermeneutic phenomenology as the methodology. Three relational themes emerged from the interview data: "Getting out of Hand," "They're in my Footstep all the Way Now," and "What's a Miranda Right"? Lastly, this article begins an exploration into the complex link between victimization and offending as it applies to one battered woman.

The authors describe and illustrate an ideographic method for the study of resilience. The method assumes that resilience is an unfolding and dynamic process in which the individual and the social environment interact to produce a life course over time. Using retrospective and prospective data, the authors present a case study of a profoundly troubled boy, first seen as a preschooler and then followed up in early adulthood with a battery of clinical interviews. The methodology presented provides a way to study resilience as a dynamic process and to reveal and make sense of counterintuitive findings. In contrast to historical or epidemiological methods, the approach also permits exploration of the role of intrapsychic processes in facilitating change.