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B cell maturation antigen (BCMA) target loss is considered to be a rare event that mediates multiple myeloma (MM) resistance to anti-BCMA chimeric antigen receptor T cell (CAR T) or bispecific T cell engager (TCE) therapies. Emerging data report that downregulation of G-protein-coupled receptor family C group 5 member D (GPRC5D) protein often occurs at relapse after anti-GPRC5D CAR T therapy. To examine the tumor-intrinsic factors that promote MM antigen escape, we performed combined bulk and single-cell whole-genome sequencing and copy number variation analysis of 30 patients treated with anti-BCMA and/or anti-GPRC5D CAR T/TCE therapy. In two cases, MM relapse post-TCE/CAR T therapy was driven by BCMA-negative clones harboring focal biallelic deletions at the TNFRSF17 locus at relapse or by selective expansion of pre-existing subclones with biallelic TNFRSF17 loss. In another five cases of relapse, newly detected, nontruncating, missense mutations or in-frame deletions in the extracellular domain of BCMA negated the efficacies of anti-BCMA TCE therapies, despite detectable surface BCMA protein expression. In the present study, we also report four cases of MM relapse with biallelic mutations of GPRC5D after anti-GPRC5D TCE therapy, including two cases with convergent evolution where multiple subclones lost GPRC5D through somatic events. Immunoselection of BCMA- or GPRC5D-negative or mutant clones is an important tumor-intrinsic driver of relapse post-targeted therapies. Mutational events on BCMA confer distinct sensitivities toward different anti-BCMA therapies, underscoring the importance of considering the tumor antigen landscape for optimal design and selection of targeted immunotherapies in MM. Tumor-intrinsic resistance mechanisms, including mutational events and immunoselection of mutant clones, were identified in 30 patients with multiple myeloma who experienced relapse after treatment with anti-BCMA CAR T cells and/or anti-BCMA bispecific T cell engagers (TCEs) or anti-GPRC5D TCE therapy.

The nursing shortage and its impact on patient care are well-documented global issues. Patients living with cancer as a chronic illness have many psychosocial problems and often lack adequate support as a result of ineffective nurse-patient communication. A review of the literature on factors influencing the delivery of psychosocial care to cancer patients indicates that the delivery of psychosocial care in routine cancer nursing within a biomedical healthcare system has not been widely explored. To explore patients' perceptions of their experiences with nurse-patient communication in an oncological clinical environment. A focused ethnographic study was undertaken in two oncology wards of a hospital in Hong Kong. Data were collected through observations of the ward environment, the activities and instances of nurse-patient communication, semi-structured interviews with patients, and a review of nursing documents. Two main themes were identified: 1. Nurses' workload and the environment and 2. Nurse-patient partnership and role expectations. Within these two themes were related subthemes on: Sympathy for the busy nurses; Prioritizing calls to the nurses; Partnership through relationship; Nurses' role in psychosocial care; and Reduction of psychosocial concerns through physical care. Many cancer patients do not expect to receive psychosocial care in the form of emotional talks or counseling from busy nurses, but appreciate the attention paid by nurses to their physiological and physical needs. Nurse-patient partnerships in cancer care may reduce the potential workload of nurses. The psychosocial needs of cancer patients could be optimized by providing good physical care through effective communication within a time-constrained oncology setting.

Ki67 is a commonly used marker of cancer cell proliferation, and has significant prognostic value in breast cancer. In spite of its clinical importance, assessment of Ki67 remains a challenge, as current manual scoring methods have high inter- and intra-user variability. A major reason for this variability is selection bias, in that different observers will score different regions of the same tumor. Here, we developed an automated Ki67 scoring method that eliminates selection bias, by using whole-slide analysis to identify and score the tumor regions with the highest proliferative rates. The Ki67 indices calculated using this method were highly concordant with manual scoring by a pathologist (Pearson's r = 0.909) and between users (Pearson's r = 0.984). We assessed the clinical validity of this method by scoring Ki67 from 328 whole-slide sections of resected early-stage, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. All patients had Oncotype DX testing performed (Genomic Health) and available Recurrence Scores. High Ki67 indices correlated significantly with several clinico-pathological correlates, including higher tumor grade (1 versus 3, P<0.001), higher mitotic score (1 versus 3, P<0.001), and lower Allred scores for estrogen and progesterone receptors (P = 0.002, 0.008). High Ki67 indices were also significantly correlated with higher Oncotype DX risk-of-recurrence group (low versus high, P<0.001). Ki67 index was the major contributor to a machine learning model which, when trained solely on clinico-pathological data and Ki67 scores, identified Oncotype DX high- and low-risk patients with 97% accuracy, 98% sensitivity and 80% specificity. Automated scoring of Ki67 can thus successfully address issues of consistency, reproducibility and accuracy, in a manner that integrates readily into the workflow of a pathology laboratory. Furthermore, automated Ki67 scores contribute significantly to models that predict risk of recurrence in breast cancer.

Background: The SUMO E3 ligase PIAS1 (Protein Inhibitor of Activated STAT1) regulates pathways such as TGFβ signaling and has been implicated in multiple cancers. However, its role in the tumor microenvironment (TME), particularly in non-malignant stromal and immune cells, remains poorly understood. This study aimed to characterize the expression and functional relevance of PIAS1 within the TME of oral squamous cell carcinoma (OSCC). Methods: PIAS1 protein expression was assessed via immunohistochemistry (IHC) on OSCC tissue microarrays. Single-cell RNA-sequencing (scRNA-seq) datasets from OSCC tumors and normal tissues were analyzed to map cell-type-specific PIAS1 expression. Downstream effects were evaluated using differential gene expression, Ingenuity Pathway Analysis (IPA), gene set enrichment analysis (GSEA), and cell–cell communication inference. Results: IHC analysis revealed that higher stromal PIAS1 levels correlated with improved survival. scRNA-seq analysis showed an increase in the proportion of PIAS1-expressing cells across most stromal and immune cell populations within OSCC-derived tumors compared to their counterparts in adjacent normal tissue. However, when comparing PIAS1-positive cells, expression levels were significantly reduced in cancer cells, CAFs, TAMs, T cells, and endothelial cells within the TME. PIAS1-positive CAFs, TAMs, and T cells exhibited activation of apoptotic and tumor-suppressive pathways, while PIAS1-negative counterparts showed enrichment of immunosuppressive signaling and immune checkpoint expression. Cell–cell communication analyses indicated that PIAS1 fosters an immune-activated TME by promoting pro-inflammatory signaling, M1-like TAM polarization, and T cell activation. Conclusions: PIAS1 expression in stromal and immune cells is associated with tumor-suppressive reprogramming of the OSCC microenvironment. These findings position PIAS1 as a potential modulator of anti-tumor immunity and candidate target for therapeutic intervention.

Despite an increase in emphasis on psychosocial care in cancer nursing, time constraints and nurses' lack of knowledge in skilled communication continue to be challenges. To examine how cancer care nurses view their communication with patients and how they deal with the psychosocial needs of patients in busy wards. A qualitative interview study. Focus groups and individual interviews were conducted with eleven hospital-based cancer nurses in Hong Kong from July 2, 2017 to January 2, 2018. A qualitative thematic analysis of the data identified three themes: 1. Intentional and unintentional psychosocial care that is secondary in focus; 2. Managing an emotionally challenged environment; 3. Mentoring and learning. Oncology settings are time-constrained, emotionally charged environments for nurses, and providing psychosocial care for patients is a secondary concern. While proactive strategies can be used to avert patient complaints, being open and attending to the individual needs of patients is equally important to avoid blocking in nurse-patient communication. Despite emotional entanglement and tensions, the positive follow-up strategies used by nurses to manage the patients' emotions and provide psychosocial care reflect good practices. Leadership and support are needed to deal with the nurses' perception that their communication training has been ineffective and their ability to manage strong emotions deficient. Communication skills, honed by making continuous opportunities to communicate available, as well as an understanding of emotional labour, need to be integrated with mindfulness in the nurses' care of themselves and their patients. Notwithstanding the importance of experience in oncology care for junior nurses, it is necessary for both junior and senior nurses to learn about and reflect upon the different forms of emotional labour if value-based care is to be provided. In addition, it is essential for junior nurses to receive continuous coaching and mentoring, and to engage in reflective learning from each clinical encounter with oncology patients.

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a novel entity characterized by its unique translocation and malignant clinical course. In this study, AFF immunohistochemistry (IHC) was performed in recurrent sinonasal papillomas for reviewing the prevalence of undiagnosed DEK::AFF2 carcinomas and to investigate the performance of AFF IHC in diagnosis of DEK::AFF2 carcinomas. Recurrent sinonasal papillomas after surgical excision in a two-decade period were retrieved. Histologic slides were reviewed for features of DEK::AFF2 carcinoma. AFF IHC was performed, and cases with any (> 1%) nuclear positivity were validated by DEK break apart fluorescence in situ hybridization. Totally 43 cases were included, comprising 28 inverted, 6 exophytic, one oncocytic, and 8 non-specified sinonasal papillomas. Five (11.6%) cases exhibited positivity to AFF IHC. Three cases exhibited patchy weak to moderate staining intensity predominantly in a granular cytoplasmic pattern. Two cases exhibited strong and diffuse (> 90%) nuclear staining. Cases showing weak staining were negative for DEK rearrangement, while those with strong staining were positive. Both cases of DEK::AFF2 carcinoma showed aggressive behavior with extensive local invasion and nodal metastasis. Background stromal plasma cells, when present, consistently showed strong and diffuse staining. AFF IHC was further performed in plasmacytoma samples as control and showed strong and diffuse immunoreactivity. A significant minority of recurrent sinonasal papillomas represent DEK::AFF2 carcinomas. Granular, cytoplasmic, or incomplete AFF staining should be considered as negative. In view of the rarity of DEK::AFF2 carcinomas, plasma cells and plasma cell neoplasms are potential for internal and surrogate external controls.

Background: Metabolomics has shown promise in gastric cancer (GC) detection. This research sought to identify whether GC has a unique urinary metabolomic profile compared with benign gastric disease (BN) and healthy (HE) patients. Methods: Urine from 43 GC, 40 BN, and 40 matched HE patients was analysed using 1 H nuclear magnetic resonance ( 1 H-NMR) spectroscopy, generating 77 reproducible metabolites (QC-RSD <25%). Univariate and multivariate (MVA) statistics were employed. A parsimonious biomarker profile of GC vs HE was investigated using LASSO regularised logistic regression (LASSO-LR). Model performance was assessed using Receiver Operating Characteristic (ROC) curves. Results: GC displayed a clear discriminatory biomarker profile; the BN profile overlapped with GC and HE. LASSO-LR identified three discriminatory metabolites: 2-hydroxyisobutyrate, 3-indoxylsulfate, and alanine, which produced a discriminatory model with an area under the ROC of 0.95. Conclusions: GC patients have a distinct urinary metabolite profile. This study shows clinical potential for metabolic profiling for early GC diagnosis.

Saccharomyces cerevisiae encodes two Pif1 family DNA helicases, Pif1 and Rrm3. Rrm3 promotes DNA replication past stable protein complexes at tRNA genes (tDNAs). We identify a new role for the Pif1 helicase: promotion of replication and suppression of DNA damage at tDNAs. Pif1 binds multiple tDNAs, and this binding is higher in rrm3 Δ cells. Accumulation of replication intermediates and DNA damage at tDNAs is higher in pif1 Δ rrm3 Δ than in rrm3 Δ cells. DNA damage at tDNAs in the absence of these helicases is suppressed by destabilizing R-loops while Pif1 and Rrm3 binding to tDNAs is increased upon R-loop stabilization. We propose that Rrm3 and Pif1 promote genome stability at tDNAs by displacing the stable multi-protein transcription complex and by removing R-loops. Thus, we identify tDNAs as a new source of R-loop-mediated DNA damage. Given their large number and high transcription rate, tDNAs may be a potent source of genome instability. The budding yeast genome encodes two Pif1 family helicases, Pif1 and Rrm3, previously shown to have distinct functions in the maintenance of telomeres and other aspects of genome stability. Here the authors identify a role for Pif1 (and Rrm3) in promoting DNA replication and suppressing R-loop mediated DNA damage at tRNA genes.

ObjectivesThis study aimed to (1) determine the knowledge level of young adults towards blood donation, and (2) to understand their donor identity and the meanings of blood donation to them.DesignA questionnaire-based cross-sectional survey.Setting and participantsUndergraduate students of a university in Hong Kong recruited by convenience sampling, at public facilities in campus such as student canteens and the Campus Blood Donor Centre of the university.Outcome measuresThe questionnaire which consisted of three parts was used for data collection. Part 1 collected sociodemographic information and items associated with blood donation; part 2 related to knowledge on blood donation and part 3 focused on blood donor identity. Univariate and multivariate logistic regression analyses were conducted to determine the OR and identify the predictors for blood donation.ResultsAmong the 542 respondents, 274 were non-blood donors and 268 were blood donors. Blood donors generally have a better knowledge towards blood donation than non-blood donors. The results of univariate analyses indicated that being a female (OR=1.99, p<0.001), aged 22 years or above (OR=234, p<0.001), studying at year 4 or 5 (OR=2.12, p=0.003), studying health-related programmes (OR=1.96, p<0.001), being registered as an organ donor (OR=6.59, p<0.001), had prior experience of receiving blood (OR=7.60, p<0.001) or prior experience of being refused for blood donation (OR=5.14, p<0.001) were significantly associated with being a blood donor. Having prior experience of receiving blood was the strongest predictor for being a blood donor, followed by being registered as an organ donor, after controlling for all other factors in the logistic regression model.ConclusionsThe findings are consistent with self-determination theory, which hypothesises that people are more likely to abide with blood donation behaviours that are internally rather than externally motivated.

Medical palpation is a task that traditionally requires a skilled practitioner to assess and diagnose a patient through direct touch and manipulation of their body. In regions with a shortage of such professionals, robotic hands or sensorized gloves could potentially capture the necessary haptic information during palpation exams and relay it to medical doctors for diagnosis. From an engineering perspective, a comprehensive understanding of the relevant motions and forces is essential for designing haptic technologies capable of fully capturing this information. This study focuses on thyroid examination palpation, aiming to analyze the hand motions and forces applied to the patient’s skin during the procedure. We identified key palpation techniques through video recordings and interviews and measured the force characteristics during palpation performed by both non-medical participants and medical professionals. Our findings revealed five primary palpation hand motions and characterized the multi-dimensional interaction forces involved in these motions. These insights provide critical design guidelines for developing haptic sensing and display technologies optimized for remote thyroid nodule palpation and diagnosis.