Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a lipid-metabolizing enzyme implicated in ferroptosis regulation and tumor aggressiveness. Although ACSL4 overexpression has been reported in various malignancies, its immunohistochemical profile in primary cutaneous melanoma has not been fully characterized. This study aimed to evaluate ACSL4 expression in melanoma compared with normal skin using quantitative digital image analysis. A total of 80 formalin-fixed paraffin-embedded samples were analyzed, including 50 primary cutaneous melanoma specimens and 30 control skin samples obtained from benign dermatologic excisions. Hematoxylin-eosin staining was used to assess histopathologic features, and ACSL4 immunostaining was performed using a standardized protocol. Quantitative evaluation was conducted with QuPath software by calculating the percentage of positive cells, mean intensity scores (0-3), and H-scores (0-300) in epidermal and dermal compartments. Group comparisons were performed using the independent t test, with p < 0.05 considered statistically significant. Control tissues exhibited minimal ACSL4 expression (epidermal H-score 12; dermal H-score 9), whereas melanoma specimens demonstrated markedly increased ACSL4 immunoreactivity. Dermal atypical melanocytic tumor cells showed the highest expression levels (mean intensity 2.10 ± 0.35; H-score 168; p < 0.001), while epidermal layers also exhibited moderately elevated staining (H-score 58; p < 0.001). Histopathologic evaluation revealed characteristic features of invasive melanoma, including atypical melanocytic nests, pagetoid spread, cytologic atypia, and architectural disorder. Overall, ACSL4 expression was significantly upregulated in primary cutaneous melanoma compared with normal skin, particularly within dermal atypical melanocytic tumor cells, suggesting that ACSL4 may contribute to melanoma biology through lipid metabolic pathways and may represent a potential biomarker of tumor aggressiveness, warranting further investigation into its diagnostic and prognostic relevance.

N-terminal acetyltransferases are emerging as potential therapeutic targets in cancer. N-alpha-acetyltransferase 30 (NAA30), which serves as the catalytic subunit of the NATC complex. However, the role of NAA30 in ovarian cancer remains unknown. In this study, we found that NAA30 expression was abnormally upregulated in ovarian cancer tissues compared to normal tissues. Functionally, NAA30 promoted cell proliferation, migration, and invasion in ovarian cancer cells. Moreover, in vivo experiments revealed that NAA30 enhanced tumor growth and intraperitoneal metastasis in mouse models. We further explored the regulatory mechanisms underlying NAA30 upregulation. Dual-luciferase assays demonstrated that the transcription factor nuclear receptor subfamily 2 group C member 2 (NR2C2) significantly enhanced the transcriptional activity of the NAA30 promoter. Besides, NR2C2 increased the migratory, invasive, and proliferative capabilities of ovarian cancer cells. Importantly, NAA30 knockdown reversed the pro-tumorigenic effects of NR2C2 overexpression on the malignant phenotype. To identify the downstream targets of NAA30, we employed IP-LC/MS and N-terminal acetylation modification omics. Actin-Related Protein 2/3 Complex Subunit 1B (ARPC1B) was identified as a direct target of NAA30. It was demonstrated that NAA30 protein binds to ARPC1B protein and that NAA30 knockdown enhanced the polyubiquitination of ARPC1B and promotes its degradation. Crucially, the re-expression of ARPC1B in NAA30-silenced cells effectively restored these malignant phenotypes. These findings highlight the critical role of the NR2C2-NAA30-ARPC1B axis in ovarian cancer progression and provide more foundation for the development of more effective treatment strategies for patients with ovarian cancer.

Recreating the human bone marrow microenvironment in vitro remains a critical challenge in advancing our understanding of hematopoiesis and its disruption in disease. Here, we present a fully tunable bone marrow model based on silk fibroin scaffolds engineered through thermo-chemical processing to replicate the mechanical and structural features of native marrow. This 3D platform integrates mesenchymal stromal cells (MSCs) and supports the functional differentiation of hematopoietic stem and progenitor cells (HSPCs) into mature megakaryocytes and platelets. RNA sequencing of MSCs cultured on physiologically tuned scaffolds revealed transcriptional programs closely aligned with native stroma, validating the fidelity of the engineered niche. The model captures essential marrow dynamics, including matrix remodeling and perfusion flow, enabling direct assessment of thrombopoietic function. To simulate fibrotic remodeling, scaffolds were functionalized with TGF-β1, inducing MSC transition into myofibroblast-like cells and recreating pathological features of myeloproliferative neoplasms. In this context, patient-derived HSPCs exhibited impaired megakaryocyte maturation and aberrant calcium signaling, partially restored by interfering with calcium flux. To quantify microenvironment-driven dysfunction, we calculated changes in megakaryocyte size distribution using a Divergence Index. Combined with the engineered niche, this functional metric offers a powerful and quantifiable platform to dissect dysregulated hematopoiesis and evaluate therapeutic strategies in patient-derived systems.

Lung cancer is one of the most aggressive malignancies worldwide. Non‑small cell lung cancer (NSCLC), in particular, is characterized by a poor 5‑year survival rate, which is largely attributable to cisplatin (DDP) resistance. However, the molecular mechanisms underlying DDP resistance are still not fully understood. Tripartite motif 46 (TRIM46) is implicated in promoting the progression of lung adenocarcinoma and enhancing chemoresistance. Nevertheless, its specific role in DDP resistance remains elusive. The present study aimed to investigate the role of TRIM46 in DDP resistance. Immunohistochemistry and TUNEL staining were employed to detect the expression of TRIM46 and apoptotic cells in tumor tissues. Lentiviruses were used to construct TRIM46 overexpression and knockdown vectors in A549 and A549/DDP cells. Cell proliferation, apoptosis and DNA damage were measured by Cell Counting Kit‑8, flow cytometry and comet assay, respectively. Subcutaneous implantation model through injection of A549/DDP cells with TRIM46 knockdown was performed in BALB/c nude female mice, followed by DDP treatment. The results revealed that TRIM46 was highly expressed in DDP‑resistant NSCLC tumor tissues and positively associated with DDP resistance. TRIM46 overexpression attenuated the DDP‑induced apoptosis and DNA damage of A549 cells. Meanwhile, the knockdown of TRIM46 enhanced the DDP‑induced apoptosis and DNA damage in A549/DDP cells. Mechanistically, TRIM46 activated the Akt signaling, thus inhibiting the expression of caspase 3 and cleaved‑caspase 3 as well as increasing the expression level of DNA repair protein RAD51. Furthermore, TRIM46 deficiency inhibited tumor growth and increased DDP sensitivity in vivo. In conclusion, the results of the present study demonstrated that TRIM46 contributed to DDP resistance by regulating the Akt signaling pathway and DNA damage, thereby offering new strategies for lung cancer therapy.

Cross-border migration presents increasing challenges to healthcare systems globally. Ensuring equitable healthcare access for immigrant populations, particularly in Southeast Asia, requires a thorough understanding of the barriers to effective service delivery. This scoping review aimed to synthesize the existing literature on the challenges related to the delivery of healthcare services to immigrant communities from Southeast Asia. While previous studies (e.g., Brandenberger et al., 2019) applied the 3C framework to migrants and refugees globally, this review generates new insights by focusing specifically on Southeast Asia, a region underrepresented in the literature. By applying the 3C model in this context, our review identifies region-specific challenges, such as immigration policies, financial barriers, and COVID-19 impacts, that extend beyond the findings of earlier global reviews.

A comprehensive search was conducted in ProQuest, PubMed, ScienceDirect, and Scopus databases on October 13, 2024, for studies published between January 1, 2011, and October 13, 2024. The search strategy used tailored keywords, including "challenges," "healthcare services," "immigrants," and "Asia." Inclusion criteria focused on peer-reviewed, English-language articles reporting on challenges in healthcare service delivery among immigrant populations in Southeast Asia. Data extraction and synthesis were guided by the 3C model: communication, continuation of care, and confidence in the healthcare system.

The search identified 656 records, of which 7 studies met the inclusion criteria after a multi-stage screening process. Key challenges identified across the included studies were: Communication barriers, including language differences, cultural misunderstandings, and limited health literacy; Issues with continuation of care, such as poor health literacy, difficulties navigating healthcare systems, barriers to accessing services (e.g., due to legal status or financial constraints), and lack of coordination between healthcare and social services; and Lack of confidence in the healthcare system, stemming from distrust, lack of understanding, and negative experiences, including perceived discrimination.

This review highlights the complex challenges in delivering healthcare services to immigrants from Southeast Asia. These challenges, encompassing communication, continuation of care, and confidence, necessitate targeted and multifaceted interventions. Addressing these issues through culturally competent care, enhanced communication strategies, and policy reforms that promote equitable access is crucial for improving the health and well-being of immigrant populations and fostering more inclusive healthcare systems within the region.

Patients with end-stage renal disease (ESRD) have compromised immune systems, possibly reducing their vaccine-induced antibody responses compared to the general population. COVID-19 remains a persistent threat, with the virus continuing to mutate into new variants. Similar to influenza, there is a possibility that COVID-19 could resurge significantly, underscoring the importance of understanding vaccine-induced immunity in vulnerable populations. This study aims to determine the immunogenicity of this group to the COVID-19 vaccine.

Haemodialysis patients receiving the Pfizer-BioNTech mRNA vaccine were followed for at least 13 months. Blood samples were collected prior to every vaccine dose and at multiple intervals thereafter. Neutralising antibodies (nAb) against SARS-CoV-2 were measured. Patients voluntarily reported any COVID-19 infection.

Between April 2021 and January 2023, 271 patients received at least one dose of the vaccine; 212 of these had at least one blood sample tested for nAb. Booster doses were given 26.2 weeks after the second dose. nAbs were detected in 16.8% of patients before vaccination. The nAb levels were higher than the non-convalescent patients after the first dose, but it was not statistically significant. Breakthrough infections were self-reported in 29.3% of patients. A significant association between breakthrough infections and history of COVID-19 infection cannot be established (p=0.188). There were 34 deaths (16.0%); 2 related to COVID-19. Younger age was associated with higher nAb reactivity post-first dose, but this difference diminished after the second dose.

Almost complete seropositivity (98.4%) was achieved after two doses of vaccine. Sustained antibody levels after the third dose suggest the value of a booster dose in protecting this vulnerable population. However, the occurrence of breakthrough infections highlights the need for continued monitoring, preventive measures, and further research to optimise vaccination strategies in haemodialysis patients.

Open-window thoracostomy offers a chance of treatment for cases of empyema thoracis not amenable for closed drainage or decortication. We review herein a collection of 12 cases based on our five years' experience in Kuala Lumpur Hospital, Malaysia performing this procedure.

Medical records of open-window thoracostomy cases performed from March 2018 till February 2023 were reviewed retrospectively. Data extracted included demographic information, indication for surgery, surgical approach, perioperative parameters, complications, and 18-months outcome. The primary end point for this study is sepsis resolution. Secondary endpoints are length of stay and spontaneous closure.

12 patients with mean age of 50.6 years underwent open-window thoracostomy. Five cases of empyema thoracis caused by bronchopleural fistula, five cases of destroyed lung and two recurrent empyema thoracis following unsuccessful decortication. All patients were extubated post-operatively except for two who required postoperative ventilatory support for two days. The primary end point was reached in all cases except one. Three complications were encountered in which blood loss exceeded 750mls.

Open-window thoracostomy may be performed safely in cases of empyema thoracis not amenable for closed drainage or decortication. Preoperative planning, preparation and counselling are vital to ensure good outcome and to manage patient's expectation.

This study aims to identify the effectiveness of asthma self-management interventions for school-aged children 6-17 years old in the US. The research questions include: (1) What interventions are conducted for asthma self-management among school children and adolescents aged 6-17 with asthma from minority families in the US? (2) Which asthma self-management intervention(s) are effective and feasible to reduce acute healthcare utilisation and improve asthma control among school-aged children 6-17 years and (3) Are there any differences in the effectiveness of self-management interventions by age groups (children 6-11 years vs adolescents 12-17 years) and by income groups (low income vs high income minority families)?

A thorough search of the literature is conducted in multiple electronic databases, such as MEDLINE, PubMed, Scopus/Embase, EbscoHost, CINAHL-full text, PsycINFO and clinical trials. This review focuses on studies of school-aged children and adolescents 6-17 years old with asthma from minority families that employ self-management intervention to enhance asthma control compared with a standard intervention/control group. The search strategies are developed following the population, intervention, comparison and outcome framework. The primary outcomes of this study are healthcare utilisation (ie, asthma-related urgent care/emergency department visits and hospitalisation), symptom control and asthma control. The process involves developing a search strategy along with inclusion and exclusion criteria, extracting relevant data, assessing the risk of bias (RoB) and analysing the data. The preferred reporting items for systematic reviews and meta-analyses guidelines will be used for reporting of the systematic review. The Cochrane Risk of Bias revised tool will be used to assess the RoB. The findings will be presented descriptively using tables, visual aids and a narrative summary. A meta-analysis will synthesise the results, exploring the impact of various interventions on asthma self-management in low-income and minority adolescents.

Ethical approval is not required for this study since this is a systematic review of existing literature. This study will synthesise evidence of asthma self-management interventions among school-aged children with asthma from minority and low-income families and identify research gaps. The findings in the meta-analysis will offer valuable insights into designing tailored evidence-based, effective, self-management interventions for school-aged children and adolescents with asthma in the future. The findings will be disseminated via peer-reviewed publications and presentations.

CRD42024567466.

Optimal antimicrobial exposure in epithelial lining fluid (ELF) is critical for meropenem efficacy in pneumonia, yet ELF pharmacokinetic data remain scarce, particularly in children. To address this, we aimed to develop a model capable of predicting meropenem concentrations in both plasma and ELF for evaluating pharmacodynamic target attainment under clinical dosing strategies.

A physiologically based pharmacokinetic (PBPK) model was developed to simulate unbound meropenem concentrations in plasma and ELF. An empirical penetration coefficient (ρ) was incorporated to link lung intracellular concentrations to ELF concentrations, modelled as a function of clinical and inflammatory covariates. Following validation, the percentage of time over a dosing interval that the free drug concentration remains above the MIC(%ƒT > MIC), of meropenem plasma and ELF were related to in-hospital mortality. Monte Carlo simulations were conducted to assess the PTA for 40%ƒT >  MIC under varying regimens, MIC ranges (0.25-16 mg/L) and penetration scenarios.

The PBPK model accurately predicted meropenem exposures in both plasma and ELF. ELF penetration was significantly influenced by physiological and pathological factors. ELF %ƒT >  MIC showed higher interindividual variability compared with that of plasma and was more strongly correlated with survival in both adult (P = 0.073) and paediatric patients (P = 0.013). Although prolonging the infusion improved ELF target attainment for susceptible pathogens (MIC ≤4 mg/L) with adequate penetration, it failed against high-MIC strains or with poor lung penetration.

These findings underscore the importance of targeting infection-site pharmacokinetics over plasma exposure for better therapeutic efficacy in pneumonia. The model can be used to optimize dosing strategies.

Due to limits in available staff and space during the COVID-19 pandemic, home monitoring programmes were introduced, reducing strain on resources, and preventing readmissions. Several hospitals included prophylaxis for venous thrombotic events (VTE), as COVID-19 appeared to be thrombogenic. Other hospitals did not, expecting patients to be more mobile while at home. Our aim was to determine whether the administration of nadroparin has led to a difference in VTE occurrence between two groups of previously included patients.

Retrospective cohort study of two cohorts included in home monitoring with the same protocol, except for nadroparin prophylaxis.

663 patients were analysed in equal groups from two hospitals. No significant difference was found in occurrence of VTE after discharge, readmissions in general or readmissions due to VTE in otherwise comparable groups.

As opposed to trials determining thrombotic prophylaxis was of benefit after discharge due to COVID-19, we found no difference between our groups. Our study was retrospective and comprised data compiled over almost two years, which provides a relatively large sample size and overview through different treatment regimes.

For the future, thrombotic prophylaxis for COVID-19 home monitoring might not be indicated and reconsidered for different home monitoring programmes.