Covalently closed circular DNA (cccDNA), a stable episomal form of the hepatitis B virus (HBV) genome, functions as the transcriptional template for viral replication and persistence, posing a major barrier to HBV cure. While host DNA repair factors such as DDB2 and DNA polymerase delta (Pol δ) have been involved in cccDNA regulation in vitro, clinical validation remains limited. This study investigated the role of DDB2 and Pol δ in cccDNA maintenance using HBV-infected cell models and liver tissues from patients with HBV-related and occult HBV infection (OBI)-associated hepatocellular carcinoma (HCC). HepG2-NTCP cells infected with HBV were transfected with siRNAs targeting DDB2 or Pol δ, followed by quantification of intracellular cccDNA using droplet digital PCR (ddPCR). In liver tissues from HBV-HCC and OBI-HCC patients, the expression of DDB2 and Pol δ was assessed, while intrahepatic HBV DNA and cccDNA were measured by qPCR and ddPCR. Serum HBcrAg levels were evaluated using the iTACT-HBcrAg assay. Knockdown of DDB2 and Pol δ significantly reduced intracellular cccDNA levels (p = 0.010 and p = 0.006, respectively). In patient tissues, intrahepatic HBV DNA and cccDNA were markedly lower in OBI-HCC compared to HBV-HCC, despite comparable DDB2 and Pol δ expression. HBcrAg was detectable in 91.3% of HBV-HCC versus only 23.8% of OBI-HCC cases (p < 0.001). DDB2 expression correlated with intrahepatic viral markers in both groups and with HBcrAg only in HBV-HCC. These findings suggest that DDB2 is involved in cccDNA persistence and represents potential therapeutic targets for both overt and occult HBV-related HCC.

Human leukocyte antigen G (HLA-G) is a nonclassical major histocompatibility complex class I molecule whose increased expression has been consistently associated with unfavorable prognosis in solid tumors and has emerged as a potential immunotherapeutic target in hematological malignancies. HLA-G exhibits limited genetic diversity and generates multiple isoforms that play a critical role in immune tolerance, being physiologically expressed in immunoprivileged tissues and aberrantly upregulated in a variety of pathological conditions, including cancer. Accumulating evidence indicates that elevated HLA-G expression contributes to tumor immune evasion and influences clinical outcomes in patients with leukemia, lymphoma, and multiple myeloma. Genetic variability within the HLA-G gene, particularly polymorphisms located in regulatory regions such as the 14-base pair insertion/deletion, has been associated with cancer susceptibility, disease progression, and adverse prognosis. In hematological malignancies, specific genotypes, including the homozygous deletion variant, have been linked to increased levels of membrane-bound and soluble HLA-G, correlating with impaired immune surveillance and reduced survival, particularly in chronic lymphocytic leukemia. Moreover, HLA-G expressions may be modulated by inflammatory cytokines, such as interferon-γ, further shaping the immunosuppressive tumor microenvironment. By functioning as a nonclassical immune checkpoint, HLA-G represents a promising target for innovative immunotherapeutic strategies, including immune checkpoint blockade combinations and chimeric antigen receptor (CAR)-T cell approaches directed against HLA-G-expressing malignant cells. In this review, we summarize current knowledge regarding HLA-G expression, genetic polymorphisms, and immunoregulatory mechanisms in hematological malignancies, highlighting their clinical and translational implications. Improved understanding of HLA-G-mediated immune modulation may contribute to the development of novel prognostic biomarkers and therapeutic strategies aimed at restoring effective antitumor immunity.

Neuroendocrine prostate cancer (NEPC) is a highly aggressive and therapy-resistant subtype of prostate cancer (PCa) that emerges following the androgen receptor (AR) targeted therapies. Identification of potential molecular drivers governing neuroendocrine differentiation (NED) and survival is critical for developing therapeutic strategies. Cancer-testis antigens of the Melanoma-associated antigen family (MAGE) are the emerging players of oncogenic regulators. However, their role in NEPC remains unexplored.

Proteomic and transcriptomic analyses were performed to identify differential expression of target proteins in NEPC. Functional characterization of MAGEA4 was performed using stable overexpression, siRNA-mediated knockdown in androgen-dependent/independent, and NEPC cell lines. For target validation, neuroendocrine markers, morphological characteristics, apoptotic signaling, oxidative pathways, and cell survival were evaluated using molecular, biochemical, and pharmacological approaches targeting SIRT1, p53 acetylation, BCL-2/BCL-XL and NRF2.

MAGEA4 was upregulated in NEPC cells and in advanced prostate cancer tissues. Overexpression of MAGEA4 induced neuroendocrine differentiation, promoted androgen-independent survival, and conferred resistance to apoptosis. Furthermore, MAGEA4 upregulated SIRT1 activity, which deacetylated p53, thereby suppressing pro-apoptotic signaling. Additionally, MAGEA4 enhanced the oxidative stress resistance through activation of the SIRT1/PGC-1α/NRF2 axis, suggesting a role in retaining the NED phenotype. In MAGEA4-positive cells, inhibition of BCL-2 and/or NRF2 attenuated the neuroendocrine characteristics, suggesting therapeutic vulnerability.

These findings highlight that MAGEA4 may contribute to neuroendocrine differentiation and survival in prostate cancer cells, and may represent a potential therapeutic vulnerability in aggressive prostate cancers.

Giant cell tumor of bone (GCTB) is an intermediate bone neoplasm defined by recurrent H3F3A mutations and limited systemic treatment options beyond denosumab. Patient-derived cancer cell lines (PDCs) offer a scalable platform for mechanistic studies and therapeutic discovery, yet the extent to which culture dimensionality alters baseline molecular states and drug response in GCTB remains unclear. Here, we performed integrated transcriptomic, proteomic, and pharmacologic profiling of thirteen patient-derived GCTB cell lines cultured under two-dimensional (2D) monolayer and three-dimensional (3D) spheroid conditions. RNA sequencing and data-independent acquisition (DIA)-based quantitative proteomics were conducted on paired cultures, and drug sensitivity was assessed using a panel of 221 anticancer agents. 3D culture reproducibly induced compact spheroid formation across all cell lines and was accompanied by broad remodeling of gene expression, protein abundance, and drug-response profiles. Unsupervised analyses consistently demonstrated that samples clustered primarily by culture condition rather than by cell-line identity at both the transcriptome and proteome levels. Although global trends were shared, a substantial fraction of molecules showed RNA-protein discordance, indicating that transcriptomic changes alone do not fully explain culture-dependent functional remodeling. Pathway analyses highlighted enrichment of extracellular matrix-related processes, stress-response programs, and metabolic regulation in 3D cultures, with several features more prominent at the protein level. Functionally, 3D culture generally reduced sensitivity to many agents while preserving compound-dependent vulnerabilities. These results establish culture dimensionality as a key determinant of therapeutic susceptibility in GCTB PDCs and support incorporating proteome-informed 3D models into translational pipelines to prioritize clinically relevant drug candidates and biomarkers.

Chronic stress resulted in poor prognosis of cancer patients in the clinic. This study aimed to explore the mechanism by which chronic stress promotes the progression of lung adenocarcinoma (LUAD) through circ_RPPH1/miR-326 axis. Chronic stress-induced LUAD in vitro and in vivo models were established in A549 cells and C57BL/6 male mice. Sucrose preference test (SPT) and forced-swimming test (FST) were used for in vivo model evaluation. qRT-PCR and western blot were used to detect mRNA and protein levels. Cell proliferation, migration and invasion were also evaluated. Luciferase reporter assay was for target gene verification. In A549 cells, acetylcholine (ACh)-induced chronic stress contributed to the upregulation of circ_RPPH1. circ_RPPH1 knockdown remitted the carcinogenic effect of chronic stress on A549 cells. circ_RPPH1 serves as a sponger of miR-326, and miR-326 downregulation neutralized the beneficial role against tumor cell function and EMT in vitro. In vivo, circ_RPPH1 knockdown reduced the tumor volume and EMT-related protein levels of tumor-bearing mice under chronic stress treatment, while miR-326 antagomir co-transfection neutralized the effect. LARP1 might be the target gene of circ_RPPH1/miR-326 axis in CUMS mice. circ_RPPH1/miR-326 axis was involved in chronic stress-promoted progression and metastasis of LUAD.

To provide an overview of the current state of international research on technology-based applications for informal caregivers of people with advanced cancer, with a particular focus on advanced breast cancer.

This scoping review was conducted in accordance with the Joanna Briggs Institute methodology and reported in line with the PRISMA-ScR guideline. The PCC framework was used to define the search terms, and develop the search strategy for the databases PubMed, CINAHL, and Web of Science. The systematic search identified 13 relevant articles describing ten different technology-based applications. One additional article was identified through a manual search.

In total, 14 studies covering ten distinct interventions were included. Some interventions were adapted from face-to-face programmes for digital delivery, whereas only a minority were explicitly informed by theoretical models from psychology or health science. The included studies addressed five main areas: informational support, mental and psychosocial support and enhancement of quality of life, physical and practical support, communication support, and preparation for caregiving and death. Evaluations reported predominantly positive findings, particularly with regard to quality of life, anxiety, depressive symptoms, and coping. However, most studies focused on advanced cancer more broadly rather than on advanced breast cancer specifically.

The reviewed literature suggests that technology-based interventions for informal caregivers of people with advanced cancer are available in several countries and address a range of support needs. However, no intervention tailored to relatives of patients with advanced breast cancer was identified as having been fully developed and evaluated. The findings highlight the need for future research on targeted, sustainable digital support for this group. The development of the Gesi-BK platform is based on the results of this scoping review.

Advances in cystic fibrosis (CF) treatment have seen more people with CF starting a family. Females with CF (FwCF) have expressed a need for improved reproductive health-related shared decision-making (SDM) with health care providers. This study explored perspectives of FwCF and clinicians on the role and implementation of SDM tools in CF reproductive health care.

We conducted qualitative semi-structured interviews with FwCF and clinicians. We recruited clinicians through professional networks and FwCF via a previous study and social media. Interviews explored experiences of SDM related to reproductive health. Participants were given examples of SDM tools and asked to consider their utility within CF care. We analyzed interview transcripts using an inductive approach, identifying key themes.

Six FwCF and 23 clinicians participated. Four themes were identified: Perceived usefulness of an SDM approach for CF reproductive health, Role of tools in facilitating SDM, Considerations for SDM tool development, and Implementation of SDM in routine CF care. Participants saw information provision as key to SDM, enhancing patient confidence to initiate and engage in conversations. Participants considered SDM tools helpful at three stages: preparing for consultations, facilitating in-consultation communication, and supporting post-consultation reflection and discussion. Trustworthy content was key to engagement. Participants felt reproductive health conversations should start in adolescence and recur throughout the life course. Clinicians highlighted the need for a service-wide culture supporting SDM.

Both groups supported early and ongoing reproductive health-related SDM. Further research should evaluate CF-specific reproductive health SDM interventions that build confidence, skills, and foster a health-service culture supportive of SDM.

Children with medical complexity are at risk of pulmonary injury due to chronic pulmonary aspiration. Our study aimed to determine the effect of multidisciplinary evaluation and periodic follow-up of aerodigestive disorders on the final status of the respiratory conditions.

Children followed for at least 1 year by the Medipol University Aerodigestive Clinic between March 2019 and August 2024 were included. Demographic data, underlying diagnoses, respiratory and nutritional status at admission, hospitalization frequency and duration, and home ventilation requirements were analyzed. Swallowing dysfunction and/or aspiration were assessed using clinical and instrumental methods. All children received tailored swallowing and nutritional therapy.

Of 89 children, 72 of them were followed for at least 1 year (12 died, 5 lost follow-up). The median follow-up period was 30 months (18-46 months). The median age during that time of admission was 30 months (11-62 months). The most common underlying conditions were neuromuscular disorders (43%), bronchopulmonary dysplasia (14%), and congenital heart disease (13%). Dysphagia was confirmed instrumentally in 61% of patients. Among tracheostomized children, 13 of 22 (60%) were successfully decannulated. Respiratory support was reduced or discontinued in 14 of 31 (45%) children. Oral feeding was achieved in 21 (29%) previously tube-fed children. Hospitalizations decreased in all but one child, and 45 (62.5%) required no hospitalization in the year following aerodigestive clinic evaluation.

A multidisciplinary aerodigestive approach improves respiratory outcomes in children with medical complexity by reducing the need for respiratory support, facilitating decannulation, and decreasing hospitalizations.

Patients with severe pulmonary embolism (PE) may experience hemodynamic instability with intubation and mechanical ventilation. However, the characteristics and outcomes of intubated PE patients have not been previously described in the literature.

We conducted a retrospective cohort study of patients requiring activation of our hospital's Pulmonary Embolism Response Team (PERT) from 2012 to 2021 who were intubated within 24 h of their acute PE diagnosis. Our primary outcome was peri-intubation hemodynamic instability and death occurring within 30 min. Our secondary outcome was peri-intubation hemodynamic instability and death within 3 h of intubation.

We included 51 patients. Within 30 min of intubation, seven (14%) patients had a new or increased vasopressor requirement, four (8%) suffered cardiac arrest, and 1 (2%) required ECMO. Within 3 h, 26 (51%) patients had a new or increased vasopressor requirement, six (12%) suffered cardiac arrest, and five (10%) required ECMO. Patients with a central PE (n = 29, 57%) were more likely to experience peri-intubation hemodynamic instability (OR 3.4, 95% CI [0.95, 13], p = 0.048). Patients who had right ventricular strain on CT (OR 3.7, 95% CI [1.01, 15], p = 0.043) or echocardiogram (OR 8.0, 95% CI [1.9, 42], p = 0.0014) were also more likely to experience hemodynamic instability.

Peri-intubation hemodynamic deterioration occurs in more than half of patients with acute PE, and severe events, like cardiac arrest, are common. Physicians should be cautious when intubating PE patients. Further research is needed to identify optimal strategies to treat PE patients who require intubation.

Introduction: Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, first emerged in Wuhan, China, in late 2019. Besides respiratory involvement, COVID-19 may cause coagulation abnormalities, leading to thromboembolic events. Mild forms of acute pancreatitis have also been reported in patients with COVID-19 pneumonia. The aim of this case report is to highlight rare extrapulmonary manifestations of SARS-CoV-2 infection, with emphasis on pancreatic involvement. Case Report: A male patient was admitted with sore throat, dry cough, and fever up to 38.0°C. He had received the first dose of the Sinopharm COVID-19 vaccine three weeks prior and was obese (BMI 44.7 kg/m²). On admission, he developed pulmonary thromboembolism. Color Doppler ultrasonography of the lower extremities showed no signs of superficial or deep vein thrombosis. On the eleventh day of treatment, laboratory tests revealed elevated serum amylase, lipase, and leukocyte count. Abdominal ultrasonography demonstrated a hyperechoic, non-enlarged pancreas, consistent with mild acute pancreatitis. Given the widespread presence of endothelial cells, SARS-CoV-2 infection may affect multiple extrapulmonary organs, including the CNS, cardiovascular system, kidneys, pancreas, liver, and gastrointestinal tract. Conclusion: SARS-CoV-2 infection may lead not only to pneumonia but also to thromboembolic complications and mild acute pancreatitis. Awareness of such rare extrapulmonary manifestations is important for timely diagnosis and management.