Penpulimab, an anti-PD-1 antibody, for heavily pretreated metastatic nasopharyngeal carcinoma: a single-arm phase II study.

Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR) per RECIST (version 1.1), as assessed by an independent radiological review committee. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). One hundred thirty patients were enrolled and 125 were efficacy evaluable. At the data cutoff date (September 28, 2022), 1 patient achieved complete response and 34 patients attained partial response. The ORR was 28.0% (95% CI 20.3-36.7%). The response was durable, with 66.8% still in response at 9 months. Thirty-three patients (26.4%) were still on treatment. The median PFS and OS were 3.6 months (95% CI = 1.9-7.3 months) and 22.8 months (95% CI = 17.1 months to not reached), respectively. Ten (7.6%) patients experienced grade 3 or higher irAEs. Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development as third-line treatment of metastatic NPC.

Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade.

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor efficacy. Targeted radionuclide therapy delivers radiation directly to tumor sites. LNC1004 is a fibroblast activation protein (FAP)-targeting radiopharmaceutical, conjugated with the albumin binder Evans Blue, which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical studies. Herein, we demonstrate that 68Ga/177Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor xenografts. Radionuclide therapy with 177Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor cells. The combination of 177Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice, with mice showing 100% tumor rejection upon rechallenge. Immunohistochemistry, single-cell RNA sequencing (scRNA-seq), and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication, CD8+ T-cell activation and expansion, M1 macrophage counts, antitumor activity of neutrophils, and T-cell receptor diversity. A preliminary clinical study demonstrated that 177Lu-LNC1004 was well-tolerated and effective in patients with refractory cancers. Further, scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade treatment. This was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell inactivation. In conclusion, our data supported the efficacy of immunotherapy combined with 177Lu-LNC1004 for cancer patients with FAP-positive tumors.

Enhanced Detection of Early Pulmonary Fibrosis Disease Using 68Ga-FAPI-LM3 PET.

Early detection of pulmonary fibrosis is a critical yet insufficiently met clinical necessity. This study evaluated the effectiveness of FAPI-LM3, a 68Ga-radiolabeled heterobivalent molecular probe that targets fibroblast activating protein (FAP) and somatostatin receptor 2 (SSTR2), in the early detection of pulmonary fibrosis, leveraging its potential for early disease identification. A bleomycin-induced early pulmonary fibrosis model was established in C57BL/6 mice for 7 days. FAP and SSTR2 expression levels were quantitatively assessed in human idiopathic pulmonary fibrosis lung tissue samples and bleomycin-treated mouse lung tissues by using western blotting, real-time quantitative PCR (RT-qPCR), and immunofluorescence techniques. The diagnostic performance of FAPI-LM3 was investigated by synthesizing monomeric radiotracers 68Ga-FAPI-46 and 68Ga-DOTA-LM3 alongside the heterobivalent probe 68Ga-FAPI-LM3. These imaging radiopharmaceuticals were used in small-animal PET to compare their uptake in fibrotic and normal lung tissues. Results indicated significant upregulation of FAP and SSTR2 at both RNA and protein levels in fibrotic lung tissues compared with that in normal controls. PET imaging demonstrated significantly enhanced uptake of the 68Ga-FAPI-LM3 probe in fibrotic lung tissues, with superior visual effects compared to monomeric tracers. At 60 min postinjection, early stage fibrotic tissues (day 7) demonstrated low-to-medium uptake of monomeric probes, including 68Ga-DOTA-LM3 (0.45 ± 0.04% ID/g) and 68Ga-FAPI-46 (0.78 ± 0.09% ID/g), whereas the uptake of the heterobivalent probe 68Ga-FAPI-LM3 (1.90 ± 0.10% ID/g) was significantly higher in fibrotic lesions than in normal lung tissue. Blockade experiments confirmed the specificity of 68Ga-FAPI-LM3 uptake, which was attributed to synergistic targeting of FAP and SSTR2. This study demonstrates the potential of 68Ga-FAPI-LM3 for early pulmonary fibrosis detection via molecular imaging, offering significant benefits over monomeric tracers 68Ga-FAPI-46 and 68Ga-DOTA-LM3. This strategy offers new possibilities for noninvasive and precise early detection of pulmonary fibrosis.

The correlation between serum angiopoietin-2 levels and acute kidney injury (AKI): a meta-analysis.

INTRODUCTION: The correlation between serum angiopoietin-2 levels and acute kidney injury (AKI) is a topic of significant clinical interest. This meta-analysis aims to provide a comprehensive evaluation of this relationship. CONTENT: A systematic search was conducted in PubMed, Embase, Web of Science, and Cochrane databases up to October 11, 2023. The included studies were evaluated using the Newcastle-Ottawa Scale (NOS) and Methodological Index for Non-Randomized Studies (MINORS). Weighted mean differences (WMD) and odds ratios (OR) were calculated using random-effects models. Sensitivity analysis, funnel plots, and Egger's test were used to assess the robustness and publication bias of the findings. Subgroup analyses were performed to explore potential variations between adults and children. SUMMARY: Eighteen studies encompassing a total of 7,453 participants were included. The analysis revealed a significant elevation in serum angiopoietin-2 levels in patients with AKI compared to those without (WMD: 4.85; 95 % CI: 0.75 to 0.27; I²=93.2 %, p<0.001). Subgroup analysis indicated significantly higher angiopoietin-2 levels in adults with AKI (WMD: 5.17; 95 % CI: 3.51 to 6.83; I²=82.6 %, p<0.001), but not in children. Additionally, high serum angiopoietin-2 levels were associated with an increased risk of AKI (OR: 1.58; 95 % CI: 1.39 to 1.8; I²=89.1 %, p<0.001). Sensitivity analysis validated the robustness of these results, showing no substantial change in the overall effect size upon the exclusion of individual studies. OUTLOOK: This meta-analysis supports a significant association between elevated serum angiopoietin-2 levels and increased risk of AKI. The observed differential association between adults and children highlights the need for further targeted research to understand these age-specific variations.

The mediating role of perceived social support on the relationship between lack of occupational coping self-efficacy and implicit absenteeism among intensive care unit nurses: a multicenter cross­sectional study.

BACKGROUND: Implicit absenteeism is very common among nurses. Poor perceived social support of intensive care unit nurses has a negative impact on their mental and physical health. There is evidence that lack of occupational coping self-efficacy can promote implicit absenteeism; however, the relationship between lack of occupational coping self-efficacy in perceived social support and implicit absenteeism of intensive care unit nurses is unclear. Therefore, this study aimed to evaluate the role of perceived social support between lack of occupational coping self-efficacy and implicit absenteeism of intensive care unit nurses, and to provide reliable evidence to the management of clinical nurses. METHODS: A cross-sectional study of 517 intensive care unit nurses in 10 tertiary hospitals in Sichuan province, China was conducted, of which 474 were valid questionnaires with a valid recovery rate of 91.6%. The survey tools included the Chinese version of Implicit Absenteeism Scale, the Chinese version of Perceived Social Support Scale, the Chinese version of Occupational Coping Self-Efficacy Scale and the Sociodemographic characteristics. Descriptive analysis and Pearson correlation analysis were performed using SPSS version 22.0, while the mediating effects were performed using AMOS version 24.0. RESULTS: The average of intensive care unit nurses had a total implicit absenteeism score of (16.87 ± 3.98), in this study, the median of intensive care unit nurses' implicit absenteeism score was 17, there were 210 intensive care unit nurses with low implicit absenteeism (44.3%) and 264 ICU nurses with high implicit absenteeism (55.7%). A total perceived social support score of (62.87 ± 11.61), and a total lack of occupational coping self-efficacy score of (22.78 ± 5.98). The results of Pearson correlation analysis showed that implicit absenteeism was negatively correlated with perceived social support (r = -0.260, P < 0.001) and positively correlated with lack of occupational coping self-efficacy (r = 0.414, P < 0.001). In addition, we found that perceived social support plays a mediating role in lack of occupational coping self-efficacy and implicit absenteeism [ß = 0.049, 95% CI of (0.002, 0.101)]. CONCLUSIONS: Intensive care unit nurses had a high level of implicit absenteeism with a moderate level of perceived social support and lack of occupational coping self-efficacy. Nursing managers should pay attention to the nurses those who were within low levels of social support and negative coping strategies, and take measures to reduce intensive care unit nurses' professional stress, minimize implicit absenteeism.

The functional role of circRNA CHRC through miR-431-5p/KLF15 signaling axis in the progression of heart failure.

Pathological myocardial hypertrophy is a common early clinical manifestation of heart failure, with noncoding RNAs exerting regulatory influence. However, the molecular function of circular RNAs (circRNAs) in the progression from cardiac hypertrophy to heart failure remains unclear. To uncover functional circRNAs and identify the core circRNA signaling pathway in heart failure, we construct a global triple network (microRNA, circRNA, and mRNA) based on the competitive endogenous RNA (ceRNA) theory. We observe that cardiac hypertrophy related circRNA (circRNA CHRC), within the ceRNA network, is down-regulated in both transverse aortic constriction (TAC) mice and Ang-II--treated primary mouse cardiomyocytes. Silencing circRNA CHRC increases cross-sectional cell area, atrial natriuretic peptide, and ß-myosin heavy chain levels in primary mouse cardiomyocytes. Further screening reveals that circRNA CHRC targets the miR-431-5p/KLF15 axis implicated in heart failure progression in vivo and in vitro. Immunoprecipitation with anti-Ago2-RNA confirms the interaction between circRNA CHRC and miR-431-5p, while miR-431-5p mimics reverse Klf15 activation caused by circRNA CHRC overexpression. In summary, circRNA CHRC attenuates cardiac hypertrophy via sponging miR-431-5p to maintain the normal level of Klf15 expression.

Development and Validation of Deep Learning Model for Intermediate-Stage Hepatocellular Carcinoma Survival with Transarterial Chemoembolization (MC-hccAI 002): a Retrospective, Multicenter, Cohort Study.

Background: There are few effective prediction models for intermediate-stage hepatocellular carcinoma (IM-HCC) patients treated with transarterial chemoembolization (TACE) to predict overall survival (OS) is available. The learning survival neural network (DeepSurv) was developed to showed a better performance than cox proportional hazards model in prediction of OS. This study aimed to develop a deep learning-based prediction model to predict individual OS. Methods: This multicenter, retrospective, cohort study examined data from the electronic medical record system of four hospitals in China between January 1, 2007, to December 31, 2016. Patients were divided into a training set(n=1075) and a test set(n=269) at a ratio of 8:2 to develop a deep learning-based algorithm (deepHAP IV). The deepHAP IV model was externally validated on an independent cohort(n=414) from the other three centers. The concordance index, the area under the receiver operator characteristic curves, and the calibration curve were used to assess the performance of the models. Results: The deepHAP IV model had a c-index of 0.74, whereas AUROC for predicting survival outcomes of 1-, 3-, and 5-year reached 0.80, 0.76, and 0.74 in the training set. Calibration graphs showed good consistency between the actual and predicted OS in the training set and the validation cohort. Compared to the other five Cox proportional-hazards models, the model this study conducted had a better performance. Patients were finally classified into three groups by X-tile plots with predicted 3-year OS rate (low: ≤ 0.11; middle: > 0.11 and ≤ 0.35; high: >0.35). Conclusion: The deepHAP IV model can effectively predict the OS of patients with IM-HCC, showing a better performance than previous Cox proportional hazards models.

Sleep health predicted glucose metabolism among pregnant women: A prospective cohort study.

AIMS: To examine whether sleep health in the first trimester could predict glucose metabolism in the second trimester. METHODS: Pregnant women (N = 127) during the first trimester were recruited (August 2022 to March 2023). Overall sleep health was assessed by the Sleep Health Index. Various dimensions of sleep health were measured using a 7-day sleep diary and questionnaires. The outcomes, including diagnosis of gestational diabetes mellitus (GDM) and HbA1c, were obtained from the medical records in the second trimester. Poisson regression analysis and multiple linear regression were used for data analysis. RESULTS: The average age of the participants was 32.6 years. The incidence of GDM was 28.3 % and the mean HbA1c was 5.2 % (33 mmol/mol). Sleep duration regularity (RR = 1.808; 95 %CI 1.023, 3.196) was associated with GDM after controlling for confounders. SHI total score (ß = -0.278; 95 %CI -0.022, -0.005) and sleep duration regularity (ß = 0.243; 95 %CI 0.057, 0.372) were associated with HbA1c. CONCLUSIONS: Worse sleep health, particularly lower sleep regularity, predicted worse glucose metabolism among pregnant women. Healthcare professional may consider adding sleep-related assessment to prenatal care. Maintaining regular sleep should be encouraged. Studies examining the impact of sleep intervention on glucose metabolism among pregnant women are warranted.

The effect of occupational coping self-efficacy on presenteeism among ICU nurses in Chinese public hospitals: a cross-sectional study.

Background: Nurses are the largest occupational group in the health field, with inestimable value in realizing universal health coverage, and nurses' physical and mental health has become an ordinary global reality. Compared with explicit absence, nurses' presenteeism has a more lasting impact and significant harm and loss. It has become an essential factor affecting nurses' physical and mental health, declining quality of healthcare services, and elevated healthcare-related risks. There is a lack of research exploring whether occupational coping self-efficacy influences nurses' presenteeism behavior, especially in less-developed regions of China. Objective: This study aimed to investigate the current status of ICU nurses' occupational coping self-efficacy and presenteeism in public hospitals in western China and to explore the impact of ICU nurses' occupational coping self-efficacy on presenteeism. Methods: A cross-sectional research design selected 722 ICU nurses in western China from January to February 2023 as survey respondents. A general information questionnaire, Occupational Coping Self-Efficacy Scale (OCSE-N), and Stanford Presenteeism Scale (SPS-6) were used. SPSS 21.0 software was used for statistical analysis. Pearson correlation analysis and multivariate hierarchical regression were used to explore the influence of ICU nurses' occupational coping self-efficacy on presenteeism. Results: A total of 722 ICU nurses completed the questionnaire. The OCSE-N score of ICU nurses was (22.24 ± 6.15), and the SPS-6 score was (16.83 ± 4.24). The high presenteeism was 67.23%. Correlation analysis showed that in ICU nurses, OCSE-N total score was negatively correlated with SPS-6 total score (r = -0.421, p < 0.05), indicating that the higher the level of occupational coping self-efficacy, the lower the presenteeism. Multiple hierarchical regression analysis showed that occupational coping self-efficacy strongly predicted presenteeism, accounting for approximately 18.35% of the total variance. Conclusion: There is a correlation between ICU nurses' occupational coping self-efficacy and presenteeism, and nurses' occupational coping self-efficacy affects presenteeism differently. Managers should pay attention to nurses' occupational coping self-efficacy to promote nurses' presenteeism reduction.

Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study.

OBJECTIVE: This study was designed to assess the efficacy and safety of cadonilimab monotherapy, a first-in-class, bi-specific PD-1/CTLA-4 antibody, in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). PATIENTS AND METHODS: This multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M-NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety. RESULTS: A total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8-25.2) months. ORR was 26.1 % (95 %CI:10.2-48.4). The ORR were 44.4 % (95 %CI: 13.7-78.8) and 14.3 % (95 %CI:1.8-42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2-73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9-45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84-9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5-91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs. CONCLUSION: Cadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.

Community structure and species diversity dynamics of a subtropical evergreen broad-leaved forest in China: 2005 to 2020.

Here, we characterize the temporal and spatial dynamics of forest community structure and species diversity in a subtropical evergreen broad-leaved forest in China. We found that community structure in this forest changed over a 15-year period. Specifically, renewal and death of common species was large, with the renewal of individuals mainly concentrated within a few populations, especially those of Aidia canthioides and Cryptocarya concinna. The numbers of individual deaths for common species were concentrated in the small and mid-diameter level. The spatial distribution of community species diversity fluctuated in each monitoring period, showing a more dispersed diversity after the 15-year study period, and the coefficient of variation on quadrats increased. In 2010, the death and renewal of the community and the spatial variation of species diversity were different compared to other survey years. Extreme weather may have affected species regeneration and community stability in our subtropical monsoon evergreen broad-leaved forests. Our findings suggest that strengthening the monitoring and management of the forest community will help better understand the long- and short-term causes of dynamic fluctuations of community structure and species diversity, and reveal the factors that drive changes in community structure.

Anoikis related genes may be novel markers associated with prognosis for ovarian cancer.

The aim of this study was to determine the prognostic significance of anoikis related genes (ARGs) in ovarian cancer (OC) and to develop a prognostic signature based on ARG expression. We analyzed cohorts of OC patients and used nonnegative matrix factorization (NMF) for clustering. Single-sample gene-set enrichment analysis (ssGSEA) was employed to quantify immune infiltration. Survival analyses were performed using the Kaplan-Meier method, and differences in survival were determined using the log-rank test. The extent of anoikis modification was quantified using a risk score generated from ARG expression. The analysis of single-cell sequencing data was performed by the Tumor Immune Single Cell Hub (TISCH). Our analyses revealed two distinct patterns of anoikis modification. The risk score was used to evaluate the anoikis modification patterns in individual tumors. Three hub-genes were screened using the LASSO (Least Absolute Shrinkage and Selection Operator) method and patients were classified into different risk groups based on their individual score and the median score. The low-risk subtype was characterized by decreased expression of hub-genes and better overall survival. The risk score, along with patient age and gender, were considered to identify the prognostic signature, which was visualized using a nomogram. Our findings suggest that ARGs may play a novel role in the prognosis of OC. Based on ARG expression, we have developed a prognostic signature for OC that can aid in patient stratification and treatment decision-making. Further studies are needed to validate these results and to explore the underlying mechanisms.

Design, Preclinical Evaluation, and Clinical Translation of 68Ga-FAPI-LM3, a Heterobivalent Molecule for PET Imaging of Nasopharyngeal Carcinoma.

Extensive research has been conducted on radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and p-Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH2 (LM3) peptides for imaging of FAP and somatostatin receptor 2 (SSTR2)-positive tumors. In this study, we designed and synthesized a FAPI-LM3 heterobivalent molecule radiolabeled with 68Ga and evaluated its effectiveness in both tumor xenografts and patients with nasopharyngeal carcinoma (NPC). Methods: The synthesis of FAPI-LM3 was based on the structures of FAPI-46 and LM3. After radiolabeling with 68Ga, its dual-receptor-binding affinity was evaluated in vitro and in vivo. Preclinical studies, including small-animal PET and biodistribution evaluation, were conducted on HT-1080-FAP and HT-1080-SSTR2 tumor xenografts. The feasibility of 68Ga-FAPI-LM3 PET/CT in a clinical setting was evaluated in patients with NPC, and the results were compared with those of 18F-FDG. Results: 68Ga-FAPI-LM3 showed high affinity for both FAP and SSTR2. The tumor uptake of 68Ga-FAPI-LM3 was significantly higher than that of 68Ga-FAPI-46 and 68Ga-DOTA-LM3 in HT-1080-FAP-plus-HT-1080-SSTR2 tumor xenografts. In a clinical study involving 6 NPC patients, 68Ga-FAPI-LM3 PET/CT showed significantly higher uptake than did 18F-FDG in primary and metastatic lesions, leading to enhanced lesion detectability and tumor delineation. Conclusion: 68Ga-FAPI-LM3 exhibited FAPI and SSTR2 dual-receptor-targeting properties both in vitro and in vivo, resulting in improved tumor uptake and retention compared with that observed with monomeric 68Ga-FAPI and 68Ga-DOTA-LM3. This study highlights the clinical feasibility of 68Ga-FAPI-LM3 PET/CT for NPC imaging.

A Pilot Study of Anlotinib as a Combination Treatment in Advanced Nasopharyngeal Carcinoma.

AIMS: To investigate the short-term objective response and treatment toxicity of anlotinib as a combination treatment in patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (RM-NPC). METHODS: Patients with RM-NPC who received anlotinib as a combination treatment between March 2021 and July 2022 were retrospectively analyzed.The efficacy and safety of anlotinib as a combination treatment were analyzed. RESULTS: A total of 17 patients with RM-NPC were included in this study. Of these patients, 2 (11.8%) had local recurrence, 4 (23.5%) had cervical lymph node recurrence, and 11 (64.9%) had distant failure. The most common metastatic site was the liver (47.1%), followed by the lung (23.5%) and bone (23.5%). Anlotinib was given as first-line treatment in 3 patients (17.6%), second lines treatment in 7 patients (41.2%), and third to six-lines treatment in 7 patients (41.2%). All patients received anlotinib combined with chemotherapy and/or immunotherapy. One patient achieved a complete response (5.9%), 7 patients had a partial response (41.2%), 5 patients had stable disease (29.4%), and 4 patients had progressive disease (23.5%). The overall disease control rate and the overall response rate were 76.5% and 47.1%, respectively. The median progression-free survival was 8.1 months, and the median overall survival was not reached. The incidence of grade 3 adverse events was 30%. No unexpected side effects or treatment-related death were observed. CONCLUSION: Anlotinib, as a combination treatment, has a promising antitumor activity and a manageable safety profile in patients with RM-NPC. Our results add to the growing evidence that supports the benefits of combining antiangiogenic drugs in RM-NPC. Randomized controlled clinical trials investigating the evaluation of anlotinib are warranted.

Decision-making experiences related to mastectomy: A descriptive qualitative study.

AIM: To obtain an in-depth understanding of women's decision-making experiences related to mastectomy. DESIGN: A descriptive qualitative interview study. METHODS: Individual semi-structured interviews were conducted face-to-face with 27 Chinese women with breast cancer who underwent mastectomy at two tertiary hospitals in mainland China between September 2020 and December 2021 after obtaining the appropriate ethical approvals. Interviews were conducted in Mandarin. Data were analysed using inductive content analysis. RESULTS: Mean age of participants was 48 years (range 31-70). Most participants had low education, low monthly family income, had a partner and health insurance, had been diagnosed with early breast cancer, and had not undergone reconstructive surgery. Six categories related to decision-making experiences emerged: (1) Emotions affecting decision-making, (2) Information seeking for decision-making, (3) Beliefs about mastectomy and the breast, (4) Participation in decision-making, (5) People who influence decision-making, and (6) Post-decision reflection. Participants did not mention the role of nurses in their decision-making process for mastectomy. CONCLUSIONS: This study adds valuable insights into the limited evidence on women's experience with decision-making about mastectomy from a Chinese perspective, which is important given the continuing high prevalence of mastectomy in many regions. Future studies from other countries and ethnic groups are recommended to gain diverse knowledge. IMPACT: The findings of this study are useful for nurses and other healthcare professionals in the multidisciplinary team to better support women with breast cancer in their decision-making process regarding mastectomy. The findings could inform future interventions to support treatment decision-making and may be relevant to women living in similar socio-medical contexts to those in mainland China. REPORTING METHOD: The study was reported following the Standards for Reporting Qualitative Research checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Kcnh2 deletion is associated with rat embryonic development defects via destruction of KCNH2­integrin ß1 complex.

The Kv11.1 potassium channel encoded by the Kcnh2 gene is crucial in conducting the rapid delayed rectifier K+ current in cardiomyocytes. Homozygous mutation in Kcnh2 is embryonically lethal in humans and mice. However, the molecular signaling pathway of intrauterine fetal loss is unclear. The present study generated a Kcnh2 knockout rat based on edited rat embryonic stem cells (rESCs). Kcnh2 knockout was embryonic lethal on day 11.5 of development due to a heart configuration defect. Experiments with human embryonic heart single cells (6.5­7 weeks post­conception) suggested that potassium voltage­gated channel subfamily H member 2 (KCNH2) plays a crucial role in the development of compact cardiomyocytes. By contrast, apoptosis was found to be triggered in the homozygous embryos, which could be attributed to the failure of KCNH2 to form a complex with integrin ß1 that was essential for preventing the process of apoptosis via inhibition of forkhead box O3A. Destruction of the KCNH2/integrin ß1 complex reduced the phosphorylation level of AKT and deactivated the glycogen synthase kinase 3 ß (GSK­3ß)/ß­catenin pathway, which caused early developmental abnormalities in rats. The present work reveals a basic mechanism by which KCNH2 maintains intact embryonic heart development.

An unsupervised real-time spike sorting system based on optimized OSort.

Objective. The OSort algorithm, a pivotal unsupervised spike sorting method, has been implemented in dedicated hardware devices for real-time spike sorting. However, due to the inherent complexity of neural recording environments, OSort still grapples with numerous transient cluster occurrences during the practical sorting process. This leads to substantial memory usage, heavy computational load, and complex hardware architectures, especially in noisy recordings and multi-channel systems.Approach. This study introduces an optimized OSort algorithm (opt-OSort) which utilizes correlation coefficient (CC), instead of Euclidean distance as classification criterion. TheCCmethod not only bolsters the robustness of spike classification amidst the diverse and ever-changing conditions of physiological and recording noise environments, but also can finish the entire sorting procedure within a fixed number of cluster slots, thus preventing a large number of transient clusters. Moreover, the opt-OSort incorporates two configurable validation loops to efficiently reject cluster outliers and track recording variations caused by electrode drifting in real-time.Main results. The opt-OSort significantly reduces transient cluster occurrences by two orders of magnitude and decreases memory usage by 2.5-80 times in the number of pre-allocated transient clusters compared with other hardware implementations of OSort. The opt-OSort maintains an accuracy comparable to offline OSort and other commonly-used algorithms, with a sorting time of 0.68µs as measured by the hardware-implemented system in both simulated datasets and experimental data. The opt-OSort's ability to handle variations in neural activity caused by electrode drifting is also demonstrated.Significance. These results present a rapid, precise, and robust spike sorting solution suitable for integration into low-power, portable, closed-loop neural control systems and brain-computer interfaces.

Readjustment of nodal staging by integrating tumor deposits and positive lymph nodes in patients with stage III colon cancer: a population-based analysis.

Whether tumor deposits (TDs) should be classified as lymph node metastasis or distant metastasis remains controversial. To address this predicament, we conducted this study to identify the predictive value of TDs on the survival of patients diagnosed with stage III colon cancer (CC). 12,904 eligible patients diagnosed with stage III CC between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The best cutoff point of TD quantity was determined based on the difference in survival. Cox proportional hazards model was employed to perform univariate and multivariate analyses. The Kaplan-Meier method and log-rank test were performed to calculate the differences between overall survival (OS). Our results showed that the number of TDs was a significant prognostic factor in patients with stage III CC (P < 0.0001). We added the number of TDs to the pN stage and devised a new pN stage, there were no significant differences in the survival of npN, except npN2a (P > 0.05). Upon re-staging to the same npN stage, the difference in survival between TDs+ and TDs- disappeared (P > 0.05). The median survival times for N2aTDs > 4 and N2bTDs > 4 were 33 and 37 months, respectively, which were significantly shorter than that of N2TDs- (65 months) and represented the worst survival rates among all groups. In conclusion, the number of TDs indicated a poor prognosis for patients with stage III CC. Incorporating TDs into the pN is feasible to predict prognosis.

Residual plasma Epstein-Barr virus DNA after intensity-modulated radiation therapy is associated with poor outcomes in nasopharyngeal carcinoma.

Aim: To investigate the effects of residual plasma Epstein-Barr virus (EBV) DNA levels after 3 months of intensity-modulated radiation therapy (IMRT) (postIMRT-EBV DNA) on prognosis in patients with nasopharyngeal carcinoma. Methods: Data from 300 patients were retrospectively collected for analysis. Results: Of these patients, 25 (8.3%) and 275 (91.7%) had positive and negative postIMRT-EBV DNA, respectively. Multivariate survival analysis showed that EBV DNA >688 IU/ml was independently associated with inferior distant metastasis-free survival (p = 0.003) and progression-free survival (p = 0.002). Moreover, postIMRT-EBV DNA was independently associated with inferior locoregional recurrence-free survival (hazard ratio: 4.325; p = 0.018), distant metastasis-free survival (hazard ratio: 10.226; p < 0.001) and progression-free survival (hazard ratio: 10.520; p < 0.001). Conclusion: Positive postIMRT-EBV DNA is a prognostic biomarker for nasopharyngeal carcinoma.

A machine learning-based PET/CT model for automatic diagnosis of early-stage lung cancer.

Objective: The aim of this study was to develop a machine learning-based automatic analysis method for the diagnosis of early-stage lung cancer based on positron emission tomography/computed tomography (PET/CT) data. Methods: A retrospective cohort study was conducted using PET/CT data from 187 cases of non-small cell lung cancer (NSCLC) and 190 benign pulmonary nodules. Twelve PET and CT features were used to train a diagnosis model. The performance of the machine learning-based PET/CT model was tested and validated in two separate cohorts comprising 462 and 229 cases, respectively. Results: The standardized uptake value (SUV) was identified as an important biochemical factor for the early stage of lung cancer in this model. The PET/CT diagnosis model had a sensitivity and area under the curve (AUC) of 86.5% and 0.89, respectively. The testing group comprising 462 cases showed a sensitivity and AUC of 85.7% and 0.87, respectively, while the validation group comprising 229 cases showed a sensitivity and AUC of 88.4% and 0.91, respectively. Additionally, the proposed model improved the clinical discrimination ability for solid pulmonary nodules (SPNs) in the early stage significantly. Conclusion: The feature data collected from PET/CT scans can be analyzed automatically using machine learning techniques. The results of this study demonstrated that the proposed model can significantly improve the accuracy and positive predictive value (PPV) of SPNs at the early stage. Furthermore, this algorithm can be optimized into a robotic and less biased PET/CT automatic diagnosis system.