Protein S-palmitoylation, and more broadly protein S-acylation when acyl donors other than palmitoyl-CoA are involved, is an emerging post-translational mechanism in cancer that dynamically regulates protein stability, membrane localization, trafficking, and signaling output. Among the zinc finger DHHC-type palmitoyl acyltransferases, ZDHHC9 has attracted increasing attention because of its expanding roles across multiple malignancies. Accumulating evidence indicates that ZDHHC9 is frequently dysregulated in cancer and contributes to tumor progression through palmitoylation-dependent regulation of proteins involved in oncogenic signaling, stress adaptation, metabolic rewiring, and immune evasion. Functionally, ZDHHC9 has been linked to the modulation of substrates such as BiP/GRP78, CD38, STAT1, PD-L1, and PCBP1, thereby influencing unfolded protein response signaling, checkpoint-related immune suppression, ferroptosis-associated pathways, and tumor cell survival. Beyond its tumor-intrinsic effects, ZDHHC9 is increasingly recognized as a regulator of the tumor immune microenvironment, with emerging evidence showing that it can suppress effector CD8+ T-cell responses and reduce sensitivity to immune checkpoint blockade in selected cancer contexts. In this review, we summarize the molecular basis of ZDHHC9, discuss its roles in tumor progression and immune regulation, and highlight current advances and challenges in therapeutic targeting. A deeper understanding of ZDHHC9-dependent palmitoylation networks may support the development of new biomarkers and precision anticancer strategies.

Machine learning models for Obstructive Sleep Apnea (OSA) diagnosis have largely inherited some structural limitations: reliance on generic, opportunistically collected feature sets; use of the Apnea-Hypopnea Index (AHI) as the sole ground truth; poor performance in multi-class severity grading; and predictions that offer clinicians no mechanistic insight. This study addresses these gaps by prospectively assembling a multi-domain dataset that, alongside established demographic, anthropometric, and questionnaire-based predictors, incorporates a panel of craniofacial and intraoral metrics specifically designed to capture the structural-anatomical contributors to OSA - integrating these into an interpretable framework for three-class severity classification evaluated against both AHI and the Oxygen Desaturation Index (ODI).

In this single-center study, 233 treatment-naïve adults from a tertiary referral cohort (61.8% severe OSA prevalence) underwent in-laboratory polysomnography (PSG). All predictor variables were collected prior to PSG outcome disclosure through a standardized clinical examination, requiring no overnight recording or specialized equipment. An Artificial Neural Network (ANN) was independently trained for three-class severity classification (No/Mild, Moderate, Severe) for each index. Model performance was evaluated on an independent test set (n = 47; 20% of the sample), with interpretability assessed using SHapley Additive exPlanations (SHAP). Comparison with an anatomy-excluded ablation model was conducted to establish the added value of the full feature set.

The AHI-based model achieved 87.2% overall accuracy (sensitivity/specificity: No/Mild 0.93/0.97, Moderate 0.80/0.91, Severe 0.88/0.93). The ODI-based model achieved 76.6% accuracy, offering reliable exclusion of severe desaturation burden (No/Mild specificity: 0.94). Univariate analyses confirmed significant associations between OSA severity and STOP-BANG score, age, BMI, neck circumference, observed apnea, loud snoring, high blood pressure, Cervico-Mental Angle, Mentocervical Distance, and submental fat (all p ≤ .034 for both indices). SHAP analysis further identified V-shaped maxillary arch, Mallampati score, increased overjet, and alcohol use as influential model predictors - several reaching high model rankings despite modest univariate significance. Notably, AHI and ODI models diverged in their feature weighting - anatomy-driven features dominated AHI prediction while body habitus and comorbidity markers dominated ODI. Against a conventional demographic and questionnaire-based ablation model, the full anatomy-inclusive ANN achieved substantially higher accuracy (87.2% vs. 72.3%), with the largest gain at the Moderate-class boundary (sensitivity: 0.80 vs. 0.58).

As a proof-of-concept, this study demonstrates that an interpretable ML framework integrating craniofacial and intraoral assessments with standard clinical predictors can classify OSA severity across three classes and provide feature-level explanations to support clinical reasoning. By developing parallel AHI and ODI models, the framework moves beyond AHI-only paradigms, though both remain frequency-based surrogates; hypoxic burden - quantifying the cumulative oxygen desaturation load per sleep period - is the more physiologically complete target toward which this line of work should progress. Findings are limited by single-center design, spectrum bias from a tertiary referral cohort, modest sample size, and absence of inter-rater reliability data. External validation in larger, more representative populations is needed to confirm the robustness and clinical utility of this approach.

Pulmonary arterial hypertension (PAH) is a complex vascular disease characterized by endothelial dysfunction, pulmonary arterial smooth muscle cell (PASMC) hyperproliferation, metabolic reprogramming, and immune-inflammatory remodeling. These pathological features are not fully explained by isolated signaling abnormalities and increasingly point to post-translational modification (PTM) crosstalk as an important layer of protein regulation. In this review, we examine the interplay among phosphorylation, ubiquitination, and SUMOylation, with a focus on how these PTMs influence protein stability, subcellular localization, and degradation in the PAH microenvironment. To distinguish disease-supported mechanisms from broader biological extrapolation, we apply a tiered evidence framework that separates crosstalk axes validated in human PAH or relevant experimental pulmonary hypertension models from those inferred from hypoxia- or cancer-related systems. Across these studies, several recurring patterns emerge, including phosphodegron-dependent substrate recognition, PTM-dependent enzyme recruitment, and context-specific coupling between SUMOylation and ubiquitin-mediated turnover. These mechanisms help explain how PTM dysregulation may weaken vasculoprotective signaling, including BMPR2-related pathways, while sustaining proliferative, inflammatory, and hypoxia-responsive signaling programs. We also discuss a conceptual systems-level model in which chronic stress reshapes the effective PTM enzyme pool through changes in enzyme abundance, substrate allocation, and subcellular compartmentalization. Finally, we consider the translational implications of targeting PTM crosstalk, including opportunities for selective intervention and current barriers related to network redundancy, off-target toxicity, and drug delivery.

Dysfunctional breathing is an important cause of breathlessness, characterised by alterations in breathing patterns. Breathing retraining (BRtr) is believed to aid patients re-establish a normal diaphragmatic breathing pattern. Structured light plethysmography was used to assess the breathing pattern of 23 children and adolescents before and after attending a specialist BRtr clinic. It showed that a 3-month physiotherapist-led BRtr programme was associated with a significant reduction in the contribution of rib cage movement to the total change in thoracic volume and respiratory rate, which was maintained when reassessed 3 months later, despite having persisted for the 3 months prior to intervention. This study provides the first objective evidence that BRtr may result in sustained improvements in breathing patterns in children and adolescents with dysfunctional breathing.

ClinicalTrials.gov, TRN: NCT04215341. Date of registration: 23 April 2015.

• Dysfunctional breathing has significant effects on children and adolescents, affecting academic and sport performance, social interactions and activities of daily living. • Breathing retraining-based physiotherapy interventions are known to improve symptoms and quality of life in children and adolescents with dysfunctional breathing.

• Breathing retraining may result in positive objective changes in the biomechanics of breathing. • Objective improvements in breathing pattern are maintained for at least 3 months after intervention.

The European Cystic Fibrosis Society (ECFS) develops education resources to support members; however, these are almost exclusively in English. Many barriers to translation exist, including cost and time. Artificial intelligence (AI) provides an opportunity to support translation and address such barriers. This study aimed to pilot the use of AI-generated translation of ECFS e-learning modules and evaluate the quality.

An AI translation program was used to create subtitles of ECFS peer-reviewed education modules. Two independent native language speakers with extensive cystic fibrosis (CF) healthcare experience were identified and tasked with reviewing, editing, and validating. This was followed by the development and circulation of an online evaluation survey assessing users' views on quality.

Education packages, each consisting of six subtitled modules, were created in three languages: Ukrainian, Romanian, and Turkish. For each language, corrections to the AI-generated translation by the independent native speakers were essential. Evaluation was conducted in two countries. Eighteen completed surveys were received. Results indicated high levels of accuracy for the final modules, and feedback was very positive regarding the utility and range of topics.

The use of novel AI-generated translation shows promise and proved quick and affordable. However, quality of translation was variable, highlighting the critical role of collaborating with native-speaking CF experts to ensure linguistic accuracy. This project highlights the importance of interdisciplinary collaborative efforts between ECFS Education, the Twinning Project, CF Europe, and patient organizations. Further, it demonstrates both the feasibility and practicality of generating effective multilingual educational modules using AI.

COVID-19 severity and survival are influenced by the host immune response to SARS-CoV-2. Programmed cell death 1 (PD-1), a key immune checkpoint, regulates T-cell activation and antiviral immune balance. Since genetic variability can modulate these responses, we investigated whether the PDCD1 polymorphisms rs11568821 C > T, rs2227982 G > A, rs2227981 G > A and rs10204525 C > T are associated with COVID-19 severity and mortality in a Brazilian cohort. A total of 366 COVID-19 patients (165 mild, 72 moderate, and 129 severe cases) were genotyped for the four PDCD1 SNPs, and their haplotype structures were estimated. Significant differences were observed in the allele frequencies of rs11568821, and in genotypes and allele frequencies of the exonic rs2227982, among mild, moderate, and severe cases. Multinomial logistic regression identified associations between rs2227982 (dominant and overdominant models) and moderate COVID-19, and between the rs2227981 AA genotype (genotypic and recessive models) and severe COVID-19. The rs10204525 polymorphism (CT genotype under genotypic dominant and overdominant models) also presented an association with severe COVID-19. However, none of these associations remained independent. Haplotype analysis identified five major haplotypes with significantly different frequencies among the groups (p = 0.02); however, no association was found between the haplotypes and disease severity or outcome. This is the first study to evaluate SNP rs2227982 in COVID-19 patients, and the first to evaluate the four aforementioned SNPs in a Brazilian population. Overall, our findings suggest that these polymorphisms, although involved in COVID-19 immunopathogenesis, are not suitable biomarkers for predicting COVID-19 severity or clinical outcomes.

Depemokimab is the first ultra-long-acting biologic with enhanced interleukin-5 (IL-5) binding affinity, high potency, and extended half-life, enabling twice-yearly dosing. Depemokimab has demonstrated efficacy and safety in patients with asthma and chronic rhinosinusitis with nasal polyps. These analyses aimed to characterize the pharmacokinetic/pharmacodynamic (PK/PD) profile of depemokimab. Data from three Phase I studies (NCT03287310/NCT05140200/NCT05602025) and four Phase III studies (SWIFT-1/-2: NCT04719832/NCT04718103; ANCHOR-1/-2: NCT05274750/NCT05281523) were used to develop a PK model for depemokimab and PK/PD model for blood eosinophil count (BEC) reduction, a key biomarker of type 2 inflammation. Participants received subcutaneous depemokimab or placebo (one dose in Phase I [2-300 mg in NCT03287310; 100 mg or 300 mg in NCT05140200/NCT05602025] and two 100 mg doses in Phase III) and ≥1 post-first-dose PK/PD (BEC) observation. PK analysis included 961 participants and PK/PD analysis included 1324 participants. Predicted geometric mean half-life was 47 days, with negligible accumulation in PK. Depemokimab 100 mg rapidly reduced BEC to <25% of baseline, with a small increase observed at the end of the 26-week dosing interval. No clinically relevant covariates were identified for either model. All participants had trough depemokimab concentrations above the half maximal effective concentration (EC₅₀) at the end of the dosing interval (90% above the EC₉₀ level). PK/PD modeling showed that single-dose depemokimab 100 mg provides durable BEC reduction throughout a 26-week dosing interval, suggesting sustained suppression of IL-5 activity. These data support twice-yearly recommended dosing for depemokimab 100 mg, with no dose adjustments required based on intrinsic or extrinsic factors.

People with dementia and their caregivers experience significant psychological distress, which may increase their vulnerability to trauma across the dementia diagnostic and caregiving trajectory. Specialist dementia helplines offer immediate emotional support, information, and signposting; however, little empirical evidence exists about how call handlers account for potential trauma in their responses.

This study aimed to examine the extent to which call handlers' responses on the United Kingdom's only 24-hour dementia helpline reflected trauma-informed (TI) principles of safety, trust, choice, collaboration, and empowerment and to describe caller characteristics and reasons for contact during the COVID-19 pandemic.

No participants were actively recruited. Instead, the study analyzed 198 anonymized, routinely collected helpline call logs (out of 200 randomly selected) drawn from 7357 calls received by Alzheimer Scotland's 24-hour helpline between April 2020 and April 2021. A retrospective deductive framework analysis mapped narrative summaries to 5 TI principles (safety, trustworthiness and transparency, choice, collaboration, and empowerment). Double‑coding and calibration were undertaken in line with established guidance on intercoder reliability for qualitative research. Descriptive statistics summarized caller characteristics and theme frequencies; no inferential testing was conducted due to the exploratory nature of the analysis, sample properties, and the subjective nature of theme ratings.

Most calls were made during daytime hours (159/198, 79.5%) and were made by carers, family members, or friends (n=179, 89.5%). Emotional support was the most frequently recorded reason for contact (91 instances), followed by carer stress (66 instances) and information on caring (51 instances). Across call handlers' responses, collaboration (126/179, 70.4%) and empowerment (108/179, 60.3%) were the most frequently observed TI principles, followed by safety (105/179, 58.7%), choice (66/179, 37.4%), and trust (56/179, 31.3%). Safety-focused responses were more prevalent in nighttime calls than daytime calls (76.9% vs 56%). Illustrative call log excerpts demonstrated empathetic listening, validation, shared problem-solving, and signposting practices aligned with TI principles.

In this exploratory retrospective evaluation, responses from a national dementia helpline commonly reflected TI principles, despite call handlers receiving primarily awareness-level TI content within their wider role preparation. Findings should be interpreted as descriptive and hypothesis-generating because they are based on call log summaries rather than recorded interactions and were obtained within the unique context of the COVID-19 pandemic. The results suggest that TI principles may be feasible and relevant in dementia helpline services and highlight the potential value of more structured approaches to TI workforce development. Future prospective research incorporating richer data sources such as recorded calls and call-reported outcomes is warranted to support service development and evaluation.

Human adenovirus (HAdV) is an important cause of respiratory infections, yet community-level burden estimates remain limited. We aimed to estimate post-pandemic HAdV burden in China. Using nationwide respiratory pathogen surveillance data and a multiplier model, we estimated the incidence of HAdV infections, symptomatic illnesses (SI), and medically attended illnesses (MAI) in China from 2023 to 2024. Age-, species-, and province-specific analyses were conducted. Uncertainty was assessed using Monte Carlo simulations. We estimated 44.21 million HAdV infections (95% UI, 26.68-77.08 million) over the 19-month study period, corresponding to an average monthly incidence of 1.58 per 1000 persons (95% UI, 1.01-2.61), equivalent to an annualized incidence of 18.96 per 1000 persons (95% UI, 12.12-31.32). The estimated average monthly incidences of SI and MAI were 0.41 (95% UI, 0.30-0.57) and 0.30 (95% UI, 0.21-0.40) per 1000 persons, corresponding to annualized incidences of 4.92 (95% UI, 3.60-6.84) and 3.60 (95% UI, 2.52-4.80) per 1000 persons, respectively. Children aged 0-4 years had the highest average monthly incidence (16.66 [95% UI, 10.26-28.54] per 1000 persons). HAdV species B showed higher incidence than species C among children aged 5-14 years. The highest incidence rates occurred in several south-central and southwestern provinces, including Hunan, Guangxi, Hubei, Guangdong, and Yunnan. HAdV imposed a substantial and under-recognized respiratory disease burden in China during the post-pandemic period. Children experienced the highest burden, and marked species-specific and geographic heterogeneity were observed. These findings provide community-based evidence to inform adenovirus surveillance and respiratory disease control strategies in China.

The COVID-19 pandemic has contributed to widespread fatigue among workers, posing a significant challenge to occupational health. Grounded in Conservation of Resources (COR) theory, this study examines the association between pandemic-related fatigue and job satisfaction and investigates whether economic security serves as a moderating factor.

A cross-sectional survey was conducted among employed residents in Ningbo, China, shortly after the lifting of COVID-19 restrictions. Data were collected using a COVID-19 Occupational Health Impact Questionnaire, which included demographic characteristics, COVID-19 history, employment status, the Fatigue Assessment Scale (FAS), a multidimensional Economic Security Index, and a job satisfaction measure. Multivariable logistic regression was used to assess associations and statistical interactions (moderation effects).

Among 1,938 participants included in the final analysis (retention rate: 98.5% of completed questionnaires), fatigue was significantly associated with lower job satisfaction (adjusted odds ratios (OR) = 0.27, 95% confidence intervals (CI): 0.22-0.34, p < 0.001). Although economic security was positively associated with job satisfaction (OR = 2.92, 95% CI: 2.39-3.58, p < 0.001), it did not significantly moderate the association between fatigue and job satisfaction (P for interaction = 0.458). The association between fatigue and lower job satisfaction was consistent across both economically secure (OR = 0.33, 95% CI: 0.24-0.44) and economically insecure (OR = 0.25, 95% CI: 0.10-0.65) subgroups.

Fatigue is strongly associated with job dissatisfaction. In this cross-sectional study, we did not find evidence that economic security moderated this association. These findings suggest that fatigue is strongly associated with job dissatisfaction across economic strata. Future research should examine whether workplace fatigue mitigation strategies are associated with in protecting employee well-being in the post-pandemic era.