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Most mature B cells can be divided into four subtypes based on the expression of the surface markers IgD and CD27: IgD + CD27 − naïve B cells, IgD + CD27 + unswitched memory B cells, IgD − CD27 + switched memory B cells, and IgD − CD27 − double‐negative (DN) B cells. Despite their small population size in normal peripheral blood, DN B cells play integral roles in various diseases. For example, they generate autoimmunity in autoimmune conditions, while these cells may generate both autoimmune and antipathogenic responses in COVID‐19, or act in a purely antipathogenic capacity in malaria. Recently, DN B cells have been identified in nasopharyngeal carcinoma and non‐small‐cell lung cancers, where they may play an immunosuppressive role. The distinct functions that DN B cells play in different diseases suggest that they are a heterogeneous B‐cell population. Therefore, further study of the mechanisms underlying the involvement of DN B cells in these diseases is essential for understanding their pathogenesis and the development of therapeutic strategies. Further research is thus warranted to characterize the DN B‐cell population in detail. Graphical Abstract This review discusses the functions of double‐negative B cells in different diseases.

The tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME. The tumor microenvironment can influence patient survival response to therapy. Here, the authors used single-cell sequencing to investigate the microenvironment of nasopharyngeal cancer and identify tumor-specific signatures in five stromal clusters of cells that may influence patient survival.

Metastasis is the biggest obstacle to esophageal squamous cell carcinoma (ESCC) treatment. Single‐cell RNA sequencing analyses are applied to investigate lung metastatic ESCC cells isolated from pulmonary metastasis mouse model at multiple timepoints to characterize early metastatic microenvironment. A small population of parental KYSE30 cell line (Cluster S) resembling metastasis‐initiating cells (MICs) is identified because they survive and colonize at lung metastatic sites. Differential expression profile comparisons between Cluster S and other subpopulations identified a panel of 7 metastasis‐initiating signature genes (MIS), including CD44 and TACSTD2, to represent MICs in ESCC. Functional studies demonstrated MICs (CD44high) exhibited significantly enhanced cell survival (resistances to oxidative stress and apoptosis), migration, invasion, stemness, and in vivo lung metastasis capabilities, while bioinformatics analyses revealed enhanced organ development, stress responses, and neuron development, potentially remodel early metastasis microenvironment. Meanwhile, early metastasizing cells demonstrate quasi‐epithelial‐mesenchymal phenotype to support both invasion and anchorage. Multiplex immunohistochemistry (mIHC) staining of 4 MISs (CD44, S100A14, RHOD, and TACSTD2) in ESCC clinical samples demonstrated differential MIS expression scores (dMISs) predict lymph node metastasis, overall survival, and risk of carcinothrombosis. CD44, TACSTD2, S100A14, and RHOD act as signatures to represent cancer‐spreading‐initiating cells in esophageal squamous cell carcinoma. These cells acquire both mobile and stational properties that flavor spreading and anchorage. High signature score predicts poor patient clinical outcomes, including worsen overall survival, increased risk of cancer‐spreading in lymph node, and increased risk of blood vessel blockage by spreading cancer cells.

Bodyweight loss is a common occurrence in Nasopharyngeal Carcinoma (NPC) patients during Radiotherapy (RT). Previous studies found that the prognostic value of percentage weight loss (pWL) during RT is not credible. We aimed to develop a novel progression predictor surrogated to pWL by modelling all bodyweight records measured during the treatment interval. This retrospective study included two independent hospitals of 624 patients. The Predicted Progression Probability (PPP) was obtained from deep learning-guided differential equation solution, model by the patient’s age, sex, body height, and the weekly measured bodyweight records. The performance of PPP in predicting disease progression was assessed, its association with prognosis and adjuvant chemotherapy response was evaluated. The PPP was learnt from the training cohort (N = 257) with 7 weeks of bodyweight records. The prediction performance was validated with 367 patients of the testing cohort sub-divided according to the number of bodyweight records found. The area under of curve for patients with 7 weeks (N = 155), 6 weeks (N = 176), and 5 weeks bodyweight records (N = 32) were 0.76, 0.73, and 0.95 respectively. PPP was significantly associated with progression-free and remained an independent prognostic factor adjusting for clinicopathologic variables in multivariate analysis in all study cohort (adjusted hazard ratio [HR] range: 2.50–7.04, all p < 0.001). Patients with high-PPP derived progression benefit from adjuvant chemotherapy (HR: 0.41–0.54, all p < 0.03), whereas those with low-PPP did not for both cohorts. The trajectory of bodyweight change during RT is more robust than the pWL to give a progression prediction after RT. The PPP is a reliable predictor for estimating the risk of residual diseases after RT course, which also helps to predict adjuvant chemotherapy response in locally advanced NPC patients.

Epstein–Barr virus, the first identified human DNA tumour virus, is detectable in more than 90% of nasopharyngeal carcinoma patients in endemic regions. The 3D chromosome conformation analysis reveals that virus‒host chromatin interactions induce the spatial reorganisation of loops and compartments, resulting in “enhancer infestation” and switch of “H3K27 bivalency” at EBV-interacting regions. Through this mechanism, EBV hijacks KDM5B, a gatekeeper of genome stability, and its binding targets, leading to aberrant activation of an EBVIR-enhancer-KDM5B signature. Cancer cells with this signature present increased MYC activation, DNA damage responses, and epigenetic plasticity of epithelial-immune dual features with metastatic potential. Our multicentre multiomics study confirms that this signature is the prerequisite for chromosome instability and can be utilised as a risk factor for distant metastasis. This study highlights a mechanism in which latent viral episomes can alter the host high-order epigenotype, promoting transcriptional rewiring and metastasis in NPC. Epstein–Barr virus - host chromatin interactions in nasopharyngeal carcinoma remain poorly understood. Here, the authors characterise the virus‒host chromatin interactions leading to genome reorganisation and identify a KDM5B-relevant signature associated with distant metastasis.

Background: Health-related quality of life (HRQoL) is important for differentiated thyroid cancer survivors, but data for Asian survivors is lacking. This study aimed to have an overview of, and identify any disease-or treatment-related factors associated with, HRQoL in Asian differentiated thyroid cancer survivors. Patients and Methods: Thyroid cancer survivors were recruited from the thyroid clinics at Queen Mary Hospital, Hong Kong from February 2016 to December 2016. All adult differentiated thyroid cancer patients with stable disease more than or equal to 1 year received a survey on HRQoL using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Thyroid cancer specific quality of life (THYCA-QoL) questionnaire. Clinical information was collected retrospectively from the computerized clinical management system. To identify factors associated with poor HRQoL, univariable and stepwise multivariable regression analysis were performed. Results: A total of 613 survivors completed the questionnaires (response rate: 82.1%; female: 80.1%; median survivorship: 7.4 years (range: 1.0-48.2 years)). The QLQ-C30 summary score mean was 84.4 (standard deviation (SD): 12.7) while the THYCA-QoL summary score mean was 39.9 (SD: 9.7). The 2 highest symptom subscales were fatigue (mean: 26.4, SD: 20.6) and insomnia (mean: 26.2, SD: 27.6). Factors associated with worse HRQoL included serum thyrotropin (TSH) greater than 1.0 mIU/L, unemployment, and concomitant psychiatric disorders. Concomitant psychiatric illness (n = 40/613, 6.5%) also showed significant association with most of the symptom and functional subscales. Conclusions: Fatigue and insomnia were the 2 most common symptoms experienced by our differentiated thyroid cancer survivors. Long-term survivorship care with monitoring serum TSH level, supporting return-to-work and screening for concomitant psychiatric disorders should be offered.

Objectives To compare the intravoxel incoherent motion (IVIM) diffusion and perfusion characteristics of nasopharyngeal carcinoma (NPC) and post-chemoradiation fibrosis to aid in their differentiation. Methods Fifty-three (64 %) patients with newly diagnosed NPC and 30 (36 %) patients with biopsy-proven post-chemoradiation fibrosis were recruited into tumour and fibrosis groups respectively. Diffusion-weighted magnetic resonance (MR) imaging was performed using 13 b values (0–1,000 s/mm 2 ). Their respective IVIM parameters ( D , pure diffusion; f , perfusion fraction; D *, pseudodiffusion coefficient) were obtained. Results D and f were significantly lower in NPC ( D  = 0.752 ± 0.194 × 10 -3  mm 2 /s, P <0.001; f  = 0.122 ± 0.095, P <0.001) than in fibrosis ( D  = 1.423 ± 0.364 × 10 -3  mm 2 /s; f  = 0.190 ± 0.120); while D * was significantly higher in NPC (111.366 ± 65.528 × 10 -3  mm 2 /s, P <0.001) than in fibrosis (77.468 ± 62.168 × 10 -3  mm 2 /s). Respective cut-off values with sensitivity, specificity and accuracy were: D  = 1.062 × 10 -3  mm 2 /s (100 %, 100 %, 100 %); f  = 0.132 (66.0 %, 100 %, 78.3 %); D * = 85.283 × 10 -3  mm 2 /s (100 %, 90.7 %, 96.4 %). Conclusion NPC and post-chemoradiation fibrosis have distinctive IVIM parameters. IVIM MR imaging is potentially useful in discrimination between NPC and fibrosis. Key Points • New MRI techniques offer greater help in the assessment of nasopharyngeal carcinoma . • Tumour and post - chemoradiation fibrosis have distinctive intravoxel incoherent motion diffusion / perfusion parameters . • Non - invasive IVIM MRI may help differentiate between tumour and fibrosis . • Pure diffusion is a robust independent discriminating factor which improves diagnostic confidence .

Hepatocellular carcinoma (HCC) is a major public health burden in Hong Kong, and chronic hepatitis B is the most common HCC etiology in our region. With the high case load, extensive local expertise on HCC has been accumulated. This article summarized local guidelines and real-life practice on HCC management in Hong Kong. For HCC surveillance, liver ultrasound and serum alpha-fetoprotein for periodic screening is recommended in viral hepatitis or cirrhotic patients, and this is adhered to in clinical practice. HCC diagnosis is not covered in local guidelines, yet our practice is in-line with regional guidelines, where diagnosis is usually achieved by cross-sectional imaging and without the need for histology. Our guidelines recommend using the Hong Kong Liver Cancer Staging for pre-treatment staging, yet we routinely use other widely-adopted systems such as the Barcelona Clinic Liver Cancer Staging and the Tumor-Node-Metastasis Staging as well. Our local guidelines have provided clear treatment algorithms for the whole range of HCC therapies, including resection, ablation, transplant, transarterial chemoembolization, transarterial radioembolization, stereotactic body radiation therapy, targeted therapy, and immunotherapy. Real-life treatment choices are largely in line with the guidelines, although treatment protocols are individualized, and availability of specific therapies can vary between centers. Overall, HCC guidelines in Hong Kong are tailored based on local expertise and our unique patient population. The guidelines are up-to-date and provide practical pathways to assist our routine practice. Regular updates of local guidelines are warranted to account for the rapidly evolving paradigm of HCC management.

Background Tuberculosis (TB) reactivation has been increasingly identified following immune checkpoint inhibitor (ICI) therapy for cancer patients. However there has been no report on TB reactivation in the gastrointestinal tract. In the report, we describe a patient who developed TB ileitis after pembrolizumab for her metastatic nasopharyngeal carcinoma (NPC). Rechallenge with pembrolizumab after its temporary interruption together with anti-TB therapy produced continuous tumor response but without further TB reactivation. Case presentation A 29-year-old lady with metastatic NPC involving the cervical nodes, lungs and bones started pembrolizumab after failure to multiple lines of chemotherapy. She complained of sudden onset of abdominal pain, vomiting and bloody diarrhea with mucus 21 months after pembrolizumab. Colonoscopy revealed terminal ileitis with multiple caseating granulomas with Langerhan cells. Serum interferon gamma release assay was strongly positive. She was treated with anti-TB medication and was later rechallenged with pembrolizumab for her progressive lung metastases without further TB relapse while her lung metastases were brought under control again. Conclusion To date, this is the first gastrointestinal TB reactivation after ICI therapy for cancer. Guidelines to screen for TB before initiation of ICIs in endemic areas should be established.

Background/Objectives: The rising prevalence of HPV-associated oropharyngeal cancer (OPC) presents a significant concern, prompting dental professionals to play an increasingly vital role in HPV vaccination and prevention within primary healthcare. This study aimed to assess the current knowledge, attitudes, and practices of dental professionals and students regarding HPV, the HPV-OPC association, and HPV vaccine communication and administration in dental settings to pinpoint areas for improvement and develop targeted interventions. Methods: This study involved a literature search in PubMed/MEDLINE, Embase, and Scopus for research outputs published from 1 January 2006 to 31 December 2024. Eligible studies examined the knowledge, perceptions, and behaviors of dental professionals and students regarding HPV and HPV-OPC. The Risk of Bias Tool was used to evaluate the bias risk in all included studies Results: Forty-two studies with a low bias risk were analyzed. While general HPV knowledge was evident in both dental practitioners and students, deficiencies in understanding HPV-OPC and vaccination were identified. Only 9% of dental practitioners discussed HPV vaccination, but future students showed greater willingness (40–80%) to engage in these discussions. Among dental professionals, common barriers included discomfort and a lack of confidence in discussing HPV vaccination. Attitudes towards administering the HPV vaccine varied between dental practitioners and students, with an interest in training programs for readiness. Liability concerns were highlighted as a significant barrier for both groups, impacting their confidence in vaccine administration. Conclusions: The findings highlight the need for strategies and areas to enhance knowledge and confidence in discussing HPV vaccines in dental primary healthcare settings, offering valuable insights for researchers and policymakers to plan programs that enhance the readiness of dental professionals to administer HPV vaccines.