Synthesis, preclinical evaluation and pilot clinical translation of [68Ga]Ga-PMD22, a novel nanobody PET probe targeting CLDN18.2 of gastrointestinal cancer.

PURPOSE: Claudin18.2 (CLDN18.2) is a novel target for diagnosis and therapy of gastrointestinal cancer. This study aimed to evaluate the safety and feasibility of a novel CLDN18.2-targeted nanobody, PMD22, labeled with gallium-68 ([68Ga]Ga), for detecting CLDN18.2 expression in patients with gastrointestinal cancer using PET/CT imaging. METHODS: [68Ga]Ga-PMD22 was synthesized based on the nanobody, and its cell binding properties were assayed. Preclinical pharmacokinetics were determined in CLDN18.2-positive xenografts using microPET/CT. Effective dosimetry of [68Ga]Ga-PMD22 was evaluated in 5 gastrointestinal cancer patients, and PET/CT imaging of [68Ga]Ga-PMD22 and [18F]FDG were performed head-to-head in 16 gastrointestinal cancer patients. Pathological tissues were obtained for CLDN18.2 immunohistochemical (IHC) staining and comparative analysis with PET/CT findings. RESULTS: Cell binding assay showed that [68Ga]Ga-PMD22 had a higher binding ability to AGSCLDN18.2 and BGC823CLDN18.2 cells than to AGS and BGC823 cells (p < 0.001). MicroPET/CT images showed that [68Ga]Ga-PMD22 rapidly accumulated in AGSCLDN18.2 and BGC823CLDN18.2 tumors, and high contrast tumor to background imaging was clearly observed. In the pilot study, the effective dose of [68Ga]Ga-PMD22 was 1.68E-02 ± 1.45E-02 mSv/MBq, and the CLDN18.2 IHC staining result was highly correlated with the SUVmax/BKGstomach of [68Ga]Ga-PMD22 (rs = 0.848, p < 0.01). CONCLUSION: A novel [68Ga]Ga-labeled nanobody probe targeting CLDN18.2, [68Ga]Ga-PMD22, was established and preliminarily proved to be safe and effective in revealing CLDN18.2-positive gastrointestinal cancer, providing a basis for the clinical translation of the agent. CLINICAL TRIAL REGISTRATION: This study was registered on the ClinicalTrials.gov (NCT05937919).

Comparison of novel PSMA-targeting [177Lu]Lu-P17-087 with its albumin binding derivative [177Lu]Lu-P17-088 in metastatic castration-resistant prostate cancer patients: a first-in-human study.

PURPOSE: Prostate-specific membrane antigen (PSMA) is a promising target for diagnosis and radioligand therapy (RLT) of prostate cancer. Two novel PSMA-targeting radionuclide therapy agents, [177Lu]Lu-P17-087, and its albumin binder modified derivative, [177Lu]Lu-P17-088, were evaluated in metastatic castration-resistant prostate cancer (mCRPC) patients. The primary endpoint was dosimetry evaluation, the second endpoint was radiation toxicity assessment (CTCAE 5.0) and PSA response (PCWG3). METHODS: Patients with PSMA-positive tumors were enrolled after [68Ga]Ga-PSMA-11 PET/CT scan. Five mCRPC patients received [177Lu]Lu-P17-087 and four other patients received [177Lu]Lu-P17-088 (1.2 GBq/patient). Multiple whole body planar scintigraphy was performed at 1.5, 4, 24, 48, 72, 120 and 168 h after injection and one SPECT/CT imaging was performed at 24 h post-injection for each patient. Dosimetry evaluation was compared in both patient groups. RESULTS: Patients showed no major clinical side-effects under this low dose treatment. As expected [177Lu]Lu-P17-088 with longer blood circulation (due to its albumin binding) exhibited higher effective doses than [177Lu]Lu-P17-087 (0.151 ± 0.036 vs. 0.056 ± 0.019 mGy/MBq, P = 0.001). Similarly, red marrow received 0.119 ± 0.068 and 0.048 ± 0.020 mGy/MBq, while kidney doses were 0.119 ± 0.068 and 0.046 ± 0.022 mGy/MBq, respectively. [177Lu]Lu-P17-087 demonstrated excellent tumor uptake and faster kinetics; while [177Lu]Lu-P17-088 displayed a slower washout and higher average dose (7.75 ± 4.18 vs. 4.72 ± 2.29 mGy/MBq, P = 0.018). After administration of [177Lu]Lu-P17-087 and [177Lu]Lu-P17-088, 3/5 and 3/4 patients showed reducing PSA values, respectively. CONCLUSION: [177Lu]Lu-P17-088 and [177Lu]Lu-P17-087 displayed different pharmacokinetics but excellent PSMA-targeting dose delivery in mCRPC patients. These two agents are promising RLT agents for personalized treatment of mCRPC. Further studies with increased dose and frequency of RLT are warranted to evaluate the potential therapeutic efficacy. TRIAL REGISTRATION: 177Lu-P17-087/177Lu-P17-088 in Patients with Metastatic Castration-resistant Prostate Cancer (NCT05603559, Registered at 25 October, 2022). URL OF REGISTRY: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05603559 .

Synthesis, preclinical, and initial clinical evaluation of integrin αVß3 and gastrin-releasing peptide receptor (GRPR) dual-targeting radiotracer [68Ga]Ga-RGD-RM26-03.

Integrin receptor αvß3 and gastrin-releasing peptide receptor (GRPR) expression of tumors could be detected using PET imaging with radiolabeled Arg-Gly-Asp (RGD) and the antagonistic bombesin analog RM26, respectively. The purpose of this study was to investigate the dual receptor-targeting property of the heterodimer RGD-RM26-03 (denoted as LNC1015), demonstrate the tumor diagnostic value of [68Ga]Ga-LNC1015 in preclinical experiments, and evaluate its preliminary clinical feasibility. METHODS: LNC1015 was designed and synthesized by linking cyclic RGD and the RM26 peptide. Preclinical pharmacokinetics were detected in a PC3 xenograft model using microPET and biodistribution studies. The clinical feasibility of [68Ga]Ga-LNC1015 PET/CT was performed in patients with breast cancer, and the results were compared with those of 18F-fluorodeoxyglucose (FDG). RESULTS: [68Ga]Ga-LNC1015 had good stability in saline for at least 2 h, and favorable binding affinity and specificity were demonstrated in vitro and in vivo. The tumor uptake and retention of [68Ga]Ga-LNC1015 during PET imaging were improved compared with its monomeric counterparts [68Ga]Ga-RGD and [68Ga]Ga-RM26 at all the time points examined. In our initial clinical studies, the tumor uptake and tumor-to-background ratio (TBR) of primary and metastatic lesions in [68Ga]Ga-LNC1015 PET/CT were significantly higher than those in [18F]FDG PET/CT, resulting in high lesion detection rate and tumor delineation. CONCLUSION: The dual targeting radiotracer [68Ga]Ga-LNC1015 showed significantly improved tumor uptake and retention, as well as lower liver uptake than [68Ga]Ga-RGD and [68Ga]Ga-RM26 monomer. The first-in-human study showed high TBRs in patients, suggesting favorable pharmacokinetics and high clinical feasibility for PET/CT imaging of cancer.

Molecular imaging of HER2 expression in breast cancer patients using a novel peptide-based tracer 99mTc-HP-Ark2: a pilot study.

BACKGROUND: Due to the temporal and spatial heterogeneity of human epidermal growth factor receptor 2 (HER2) expression in breast tumors, immunohistochemistry (IHC) cannot accurately reflect the HER2 status in real time, which may cause misguided treatment decisions. HER2-specific imaging can noninvasively determine HER2 status in primary and metastatic tumors. In this study, HER2 expression in breast cancer patients was determined in vivo by SPECT/CT of 99mTc-HP-Ark2, comparing with PET/CT of 18F-FDG lesion by lesion. METHODS: A novel HER2-targeted peptide probe 99mTc-HP-Ark2 was constructed. Biodistribution and nanoScan SPECT/CT imaging were performed in mice models. The correlation between the quantified tumor uptake and HER2 expression in tumor cells was analyzed. In the pilot clinical study, a total of 34 breast cancer patients (mean age ± SD: 49 ± 10 y) suspected of having breast cancer according to mammography or ultrasonography were recruited at Peking Union Medical College Hospital, and 99mTc-HP-Ark2 SPECT/CT and 18F-FDG PET/CT were carried out with IHC and fluorescence in situ hybridization as validation. RESULTS: Small animal SPECT/CT of 99mTc-HP-Ark2 clearly identified tumors with different HER2 expression. The quantified tumor uptake and tumor HER2 expression showed a significant linear correlation (r = 0.932, P < 0.01). Among the 36 primary lesions in the 34 patients, when IHC (2 +) or IHC (3 +) was used as the positive evaluation criterion, 99mTc-HP-Ark2 SPECT/CT imaging with a tumor-to-background ratio of 1.44 as the cutoff value reflected the HER2 status with sensitivity of 89.5% (17/19), specificity of 88.2% (15/17) and accuracy of 88.9% (32/36), while the 18F-FDG PET/CT showed sensitivity of 78.9% (15/19), specificity of 70.6% (12/17) and accuracy of 75.0% (27/36). In particular, 100% of IHC (3 +) tumors were all identified by 99mTc-HP-Ark2 SPECT/CT imaging. CONCLUSION: 99mTc-HP-Ark2 SPECT/CT can provide a specific, noninvasive evaluation of HER2 expression in breast cancer, showing great potential to guide HER2-targeted therapies in clinical practice. CLINICALTRIALS: gov Trial registration: NCT04267900. Registered 11th February 2020. Retrospectively registered, https://www. CLINICALTRIALS: gov/ct2/results?pg=1&load=cart&id=NCT04267900 .

A prospective head-to-head comparison of [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-11 PET/CT in patients with primary prostate cancer.

PURPOSE: We aimed to compare the diagnostic performance and biodistribution of two similar PET agents, [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-11, in the same group of primary prostate cancer (PCa) patients. METHODS: Fifty patients with untreated, histologically confirmed PCa by needle biopsy were enrolled. Each patient underwent [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-11 PET/CT within a week. In addition to visual analysis, the standardized uptake value (SUV) was measured for semiquantitative comparison and correlation analysis. RESULTS: [68Ga]Ga-P16-093 PET/CT detected more positive tumors than [68Ga]Ga-PSMA-11 PET/CT (202 vs. 190, P = 0.002), both for intraprostatic lesions (48 vs. 41, P = 0.016) and metastatic lesions (154 vs. 149, P = 0.125), especially for intraprostatic lesions in low- and intermediate-risk PCa patients (21/23 vs. 15/23, P = 0.031). Furthermore, [68Ga]Ga-P16-093 PET/CT exhibited a significantly higher SUVmax for most matched tumors (13.7 ± 10.2 vs. 11.4 ± 8.3, P < 0.001). For normal organs, [68Ga]Ga-P16-093 PET/CT showed significantly lower activity in the kidney (SUVmean: 20.1 ± 6.1 vs. 29.3 ± 9.1, P < 0.001) and urinary bladder (SUVmean: 6.5 ± 7.1 vs. 20.9 ± 17.4, P < 0.001), but displayed a higher uptake in the parotid gland (SUVmean: 8.7 ± 2.6 vs. 7.6 ± 2.1, P < 0.001), liver (SUVmean: 7.0 ± 1.9 vs. 3.7 ± 1.3, P < 0.001), and spleen (SUVmean: 8.2 ± 3.0 vs. 5.2 ± 2.2, P < 0.001) than [68Ga]Ga-PSMA-11 PET/CT. CONCLUSION: [68Ga]Ga-P16-093 PET/CT demonstrated higher tumor uptake and better tumor detectability than [68Ga]Ga-PSMA-11 PET/CT, especially in low- and intermediate-risk PCa patients, which indicated that [68Ga]Ga-P16-093 may serve as an alternative agent for detection of PCa. TRIAL REGISTRATION: 68Ga-P16-093 and 68Ga-PSMA-11 PET/CT Imaging in the Same Group of Primary Prostate Cancer Patients (NCT05324332, Registered 12 April 2022, retrospectively registered). URL OF REGISTRY: https://clinicaltrials.gov/ct2/show/NCT05324332 .

The trajectories and associations of insomnia symptoms with addictive behaviours in adolescents: A two-year longitudinal study.

Insomnia displays heterogeneous trajectories across adolescence, which may induce addictive behaviours, including internet gaming disorder and substance use. This study aimed to investigate the latent trajectory classes of insomnia symptoms over 2 years and to examine the associations between insomnia trajectories and these addictive behaviours. Participants were 910 adolescents from six middle schools in Shanghai, China (52.7% males; mean age = 13.17 years). The three-wave survey measured insomnia symptoms, internet gaming disorder, substance use, depressive symptoms, and sociodemographic characteristics from 7th to 9th grade. Latent class growth modelling was performed to identify the latent trajectory classes of insomnia symptoms. Then multivariable logistic regressions were conducted within the best-fitting latent class growth model to examine the associations of insomnia trajectories with internet gaming disorder and substance use. Two latent trajectory classes of insomnia symptoms were recognised: the non-insomnia group (71.8%) and the insomnia group (28.2%). In the multivariable analysis controlling for baseline demographic variables and depressive symptoms, the insomnia group had a higher risk of developing internet gaming disorder (OR = 2.203 [95% CI: 1.258-3.858]) and substance use (OR = 2.215 [95% CI: 1.324-3.705]) compared with the non-insomnia group. These findings add to a growing body of research on heterogeneous trajectories of insomnia symptoms during adolescence, suggesting that intervention strategies are needed to target the characteristics or developmental patterns of different insomnia subgroups. The ultimate goal is to mitigate the impact of insomnia symptoms on adolescent addictive behaviours.

The information-motivation-behavioral skills (IMB) model of antiretroviral therapy (ART) adherence among people living with HIV in Shanghai.

The Information-Motivation-Behavioral skills (IMB) model of antiretroviral therapy (ART) adherence was applied in people living with HIV/AIDS in Shanghai, China to understand how adherence-related information, motivation and behavioral skills would affect ART adherence. The LifeWindows Information-Motivation-Behavioral Skills ART Adherence Questionnaire (LW-IMB-AAQ) was translated into Chinese and used. The IMB model was then implemented by testing standardized path estimates with standard model fitness indices in the participants. 426 participants from 11 community centres in Putuo district of Shanghai were recruited, of which 95.3% reported a high level of adherence (>95% adherence). The fitness indices of the final adjusted model were χ2 = 6.110, df = 7, p = 0.527(>0.05), CFI = 1.000(>0.9) and RMSEA = 0.000 (<0.08). In the model, information, which was separated into two sections (the perceived effect of ART on health and knowledge about ART medication), had an indirect effect on the ART adherence through behavioral skills, while motivation did not have such an effect. Neither information nor motivation had a direct effect on ART adherence. In addition, motivation was related to the two sections of information. The feasibility of the IMB model of ART adherence is verified by its application to predictive of adherence-related behaviors among HIV+ patients in this study.

Relationships of work stress and interpersonal needs with industrial workers' mental health: a moderated mediation model.

OBJECTIVES: This study explores whether feelings of defeat (i.e., a sense of failed struggle and losing rank; referred to as defeat for simplicity) mediated the effect of work stress on depression/anxiety, the effect of interpersonal needs on depression/anxiety for Chinese industrial workers, and the possible moderating role of social support. METHOD: A cross-sectional study was conducted in Shenzhen, China in 2019, in total, 2023 industrial workers (of 2700 invited; response rate = 75%) completed a self-administered survey consisted of Job Stress Scale, Interpersonal Needs Questionnaire, Defeat Scale, Centre for Epidemiological Studies Depression Scale, Generalized Anxiety Disorder Scale, two face-valid questions for social support, as well as sociodemographic information. Moderated mediation model was tested and loop plots were applied to probe into the conditional effects of work and interpersonal stress on depression and anxiety symptoms. RESULT: Both the direct and indirect effect of work stress on depression and anxiety through defeat were significant (Work stress→ Depression: B = 0.035, p < .001, Work stress→ Defeat→ Depression: B = 0.034, p < .001; Work stress→ Anxiety: B = 0.038, p < .001, Work stress→ Defeat→ Anxiety: B = 0.045, p < .001). Meanwhile, defeat mediated the relationship of interpersonal needs with depression partially and the relationship of interpersonal needs with anxiety totally (Interpersonal needs→ Anxiety: B = 0.133, p < .001, Interpersonal needs→ Defeat→ Anxiety: B = 0.010, p = .537). Social support moderated the indirect path between interpersonal needs and depression/anxiety and buffered the effect. CONCLUSION: The mediating role of defeat and the moderator role of social support in the relationship between stress and depression/anxiety were confirmed in industrial workers. Workers who reported more work and interpersonal stress would report more defeat feelings, and then exhibited more depression and anxiety symptoms; this mediation effect was stronger for those who had lower social support, respectively.

A model to predict adherence to antiretroviral therapy among people living with HIV.

OBJECTIVES: Suboptimal adherence to antiretroviral therapy (ART) dramatically hampers the achievement of the UNAIDS HIV treatment targets. This study aimed to develop a theory-informed predictive model for ART adherence based on data from Chinese. METHODS: A cross-sectional study was conducted in Shenzhen, China, in December 2020. Participants were recruited through snowball sampling, completing a survey that included sociodemographic characteristics, HIV clinical information, Information-Motivation-Behavioural Skills (IMB) constructs and adherence to ART. CD4 counts and HIV viral load were extracted from medical records. A model to predict ART adherence was developed from a multivariable logistic regression with significant predictors selected by Least Absolute Shrinkage and Selection Operator (LASSO) regression. To evaluate the performance of the model, we tested the discriminatory capacity using the concordance index (C-index) and calibration accuracy using the Hosmer and Lemeshow test. RESULTS: The average age of the 651 people living with HIV (PLHIV) in the training group was 34.1±8.4 years, with 20.1% reporting suboptimal adherence. The mean age of the 276 PLHIV in the validation group was 33.9±8.2 years, and the prevalence of poor adherence was 22.1%. The suboptimal adherence model incorporates five predictors: education level, alcohol use, side effects, objective abilities and self-efficacy. Constructed by those predictors, the model showed a C-index of 0.739 (95% CI 0.703 to 0.772) in internal validation, which was confirmed be 0.717 via bootstrapping validation and remained modest in temporal validation (C-index 0.676). The calibration capacity was acceptable both in the training and in the validation groups (p>0.05). CONCLUSIONS: Our model accurately estimates ART adherence behaviours. The prediction tool can help identify individuals at greater risk for poor adherence and guide tailored interventions to optimise adherence.

A prospective head-to-head comparison of 68 Ga-NOTA-3P-TATE-RGD and 68 Ga-DOTATATE in patients with gastroenteropancreatic neuroendocrine tumours.

PURPOSE: The aim of this study was to compare 68 Ga-NOTA-3P-TATE-RGD, a dual somatostatin receptor 2- and integrin αVß3-targeting tracer, to 68 Ga-DOTATATE in a single group of patients with gastroenteropancreatic (GEP)-neuroendocrine tumours (NETs). METHODS: Thirty-five patients with histologically confirmed GEP-NETs (5 grade 1, 28 grade 2, and 2 grade 3 tumours) were prospectively enrolled with informed consent. The primary tumour mainly originated from the pancreas and rectum. All patients were scanned with both 68 Ga-NOTA-3P-TATE-RGD PET/CT and 68 Ga-DOTATATE PET/CT within a week and compared on a head-to-head basis. Sixteen patients also had conventional 18F-FDG PET/CT. Images were evaluated semi-quantitatively using maximum standardized uptake values (SUVmax) of tumour and tumour-to-background ratio. RESULTS: All patients had at least one positive lesion on each of the two scans. A total of 1190 and 1106 lesions were detected on 68 Ga-NOTA-3P-TATE-RGD images and 68 Ga-DOTATATE images, respectively (P = 0.152). 68 Ga-NOTA-3P-TATE-RGD PET/CT revealed significantly more lesions in the liver than 68 Ga-DOTATATE PET/CT (634 vs. 532, P = 0.021). Both tracers produced comparable results for detecting primary tumours (20 vs. 20, P = 1.000), lymph node metastases (101 vs. 102, P = 0.655), and bone metastases (381 vs. 398, P = 0.244). The tumour SUVmax in 12 patients was significantly higher for 68 Ga-NOTA-3P-TATE-RGD than for 68 Ga-DOTATATE (27.2 ± 13.6 vs. 19.5 ± 10.0, P < 0.001); among them, 9 had 18F-FDG PET/CT and all were found to be FDG-positive. The remaining 23 patients had significantly higher 68 Ga-DOTATATE uptake than 68 Ga-NOTA-3P-TATE-RGD uptake (22.3 ± 16.4 vs. 11.9 ± 7.5, P < 0.001); among them, 7 had 18F-FDG PET/CT and 6 were FDG-negative. Generally, 68 Ga-DOTATATE demonstrated higher tumour SUVmax than 68 Ga-NOTA-3P-TATE-RGD (20.8 ± 16.0 vs. 14.2 ± 8.9, P < 0.001), including primary tumours, liver lesions, lymph node lesions, and bone lesions. However, the tumour-to-background ratio of liver lesions was significantly higher when using 68 Ga-NOTA-3P-TATE-RGD compared with that when using 68 Ga-DOTATATE (8.4 ± 5.5 vs. 4.7 ± 3.7, P < 0.001). CONCLUSION: 68 Ga-NOTA-3P-TATE-RGD performed better than 68 Ga-DOTATATE in detection of liver metastases with a higher tumour-to-background ratio. Moreover, 68 Ga-NOTA-3P-TATE-RGD tended to demonstrate higher uptake over 68 Ga-DOTATATE in FDG-avid NETs. TRIAL REGISTRATION: Dual SSTR2 and Integrin αvß3 Targeting PET/CT Imaging (NCT02817945, registered 5 November 2018). URL OF REGISTRY: https://clinicaltrials.gov/ct2/show/NCT02817945.

The association between entrapment and depression among migrant workers in China: a social rank theory based study.

BACKGROUND: Migrant workers are a group susceptible for depression evolution due to occupational maladaptive triggers. The social rank theory illustrates the pathology process from defensive adaptation to depression, pointing out the early prevention of depression by discovering entrapment. This study aims to reveal the relationship between migrant workers' entrapment and depressive symptoms. METHODS: A total of 1805 migrant workers in Shenzhen were recruited by stratified multi-stage sampling. Sample's demographic, behavioral and psychosocial characteristics were described and analyzed to reveal the relationship between entrapment and depressive symptoms. The Receiver Operator Characteristic was performed to find the optimal cut-off point of Entrapment Scale for predicting depressive symptoms. RESULTS: In the binary logistic regression of sociodemographic variables, migrant workers who were married (univariate odds ratio (ORu) = 0.69, 95% Confidence Interval (CI) = 0.56-0.84), owned 1 or 2 children (ORu = 0.71, 95% CI = 0.58-0.86), had been working over 10 years (ORu = 0.71, 95% CI = 0.54-0.95), earned > 4999 yuan per month (ORu = 0.68, 95% CI = 0.47-0.99; multivariate odds ratio (ORm) = 0.57, 95% CI = 0.38-0.87) or with low risks of alcohol use disorders (ORu = 0.51, 95% CI = 0.34-0.75) had lower risks of depressive symptoms. After adjusted the aforementioned significant sociodemographic variables, migrant workers with severer entrapment were more likely to have depressive symptoms (adjusted odds ratio (ORa) = 1.13, 95% CI = 1.12-1.15). Besides, the study proved the reliability and validity of the Chinese version Entrapment Scale, preferring a two-dimensional structure, and 11 was the optimal cut-off value of this scale for predicting depressive symptoms among migrant workers. CONCLUSIONS: This result indicates the potential value of entrapment according to the social rank theory on facilitating early prevention of migrant works' depression and the application value of Entrapment Scale for effectively measuring mental status among migrant workers.

Adaptive symbolic transfer entropy and its applications in modeling for complex industrial systems.

Directed coupling between variables is the foundation of studying the dynamical behavior of complex systems. We propose an adaptive symbolic transfer entropy (ASTE) method based on the principle of equal probability division. First, the adaptive kernel density method is used to obtain an accurate probability density function for an observation series. Second, the complete phase space of the system can be obtained by using the multivariable phase space reconstruction method. This provides common parameters for symbolizing a time series, including delay time and embedding dimension. Third, an optimization strategy is used to select the appropriate symbolic parameters of a time series, such as the symbol set and partition intervals, which can be used to convert the time series to a symbol sequence. Then the transfer entropy between the symbolic sequences can be carried out. Finally, the proposed method is analyzed and validated using the chaotic Lorenz system and typical complex industrial systems. The results show that the ASTE method is superior to the existing transfer entropy and symbolic transfer entropy methods in terms of measurement accuracy and noise resistance, and it can be applied to the network modeling and performance safety analysis of complex industrial systems.

Neoadjuvant BRAF and MEK inhibitor therapy elicits pathological complete response in stage IIIA non-small cell lung cancer harboring BRAF V600E mutation: A case report.

In recent years, significant improvement has been made in the management of non-small cell lung cancer (NSCLC), primarily driven by advances in targeted therapy and immunotherapy. Research on neoadjuvant targeted therapy has also experienced considerable development, primarily directed towards NSCLC harboring epidermal growth factor receptor or anaplastic lymphoma kinase mutations. Nevertheless, there remains a dearth of studies investigating neoadjuvant targeted therapy in the context of BRAF (V-Raf murine sarcoma viral oncogene homolog B) V600E mutant NSCLC. Herein, we describe the clinical trajectory of a stage IIIA NSCLC patient who underwent a two-month course of neoadjuvant targeted therapy comprising BRAF and MEK (mitogen-activated extracellular signal-regulated kinase) inhibitors prior to surgical intervention, and subsequent postoperative evaluation unveiled a pathological complete response. The case reported here indicates the efficacy and safety of combining BRAF and MEK inhibitors as neoadjuvant targeted therapy in BRAF V600E-mutant NSCLC and suggests the potential viability of such a therapeutic modality in improving treatment outcomes in this subset of NSCLC.

A Delphi Study to Construct an Index of Practice for Community Nurses Providing Transitional Home Care for Patients with Chronic Diseases.

Community nurses play a key role in providing continuous home care for patients with chronic diseases. However, a perfect system of responsibilities and requirements has not yet been formed, and nurses cannot provide high-quality nursing services for home-based patients. We attempted to construct an index of the scope of practice for community nurses providing home-based transitional care for patients with chronic diseases and to guide nurses in playing an active role in transitional care work. From March to May 2023, 14 representative community nurses from the Shanghai Community Health Service Center were selected for group interviews and 2 rounds of Delphi consultation. A total of 14 valid questionnaires were collected. The authority coefficients were 0.94 and 0.93, and the Kendall coefficients were 0.56 and 0.59 for the 2 rounds of expert consultation (P < .05). Finally, an index system, including 6 primary indices (transitional caring provider, patient self-management facilitator, community group intervention organizer, home caregiver supporter, family physician team collaborator and supervisor of home medical equipment use, and medical waste disposal) was constructed for community nurses involved in providing home-based transitional care for patients with chronic diseases. The weight values of the 6 indices were 0.19, 0.17, 0.21, 0.13, 0.14 and 0.16, respectively (CR = 0.035, and the consistency test was passed), and 16 secondary indicators and 42 tertiary indicators were identified. In this Delphi study, an index system that can be used to determine community nurses' roles in providing home-based transitional and continuous care for patients with chronic diseases was successfully established. The index system is considered reliable and easy to use and will provide a meaningful reference for community nurses and policy-makers.

68 Ga-FAPI-04 PET/CT in Assessment of Fibroblast Activation in Keloids : A Prospective Pilot Study.

PURPOSE: Keloids are benign fibroproliferative disorders characterized by the massive proliferation of fibroblasts. Fibroblast activation plays a key role in the invasive growth of keloids. Therefore, a prospective pilot study was conducted to explore the value of 68 Ga-FAPI-04 PET/CT in the assessment of keloids activity. PATIENTS AND METHODS: Twenty-five patients with keloid were enrolled to conduct 68 Ga-FAPI-04 PET/CT. All patients accepted surgery to remove part of the lesions within 1 week. SUV mean and SUV max were measured for semiquantitative analysis and compared with the Vancouver Scar Scale, Laser Speckle Contrast Imaging, pathology, and immunohistochemical stains. RESULTS: A total of 123 lesions were detected in 25 patients, most of which were distributed in the anterior chest wall. The 68 Ga-FAPI-04 uptake was significantly different at different sites ( P < 0.0001). There was uptake heterogeneity within the keloid lesions, and a significant difference was found between the edge and center of some large lesions. The SUV max of 68 Ga-FAPI-04 showed significantly correlation with the Vancouver Scar Scale ( r = 0.565, P < 0.0001) moderately and the Laser Speckle Contrast Imaging parameters mildly. The SUV max of 68 Ga-FAPI-04 had a moderate correlation with FAPI expression ( r = 0.520, P = 0.022). Moreover, collagen, fibroblast activator protein, and Ki-67 expression were found higher at the edges of keloid tissue than in the center. CONCLUSIONS: 68 Ga-FAPI-04 PET/CT can reflect the distribution characteristics of activated fibroblasts in keloid tissue and may provide a novel method for keloid evaluation for further fibroblast-related therapies.

Evaluation of the psychometrics of the Social Impact Scale and its association with depression among asymptomatic COVID-19 carriers.

BACKGROUND: COVID-19 carriers experience psychological stresses and mental health issues such as varying degrees of stigma. The Social Impact Scale (SIS) can be used to measure the stigmatisation of COVID-19 carriers who experience such problems. AIMS: To evaluate the reliability and validity of the Chinese version of the SIS, and the association between stigma and depression among asymptomatic COVID-19 carriers in Shanghai, China. METHOD: A total of 1283 asymptomatic COVID-19 carriers from Shanghai Ruijin Jiahe Fangcang Shelter Hospital were recruited, with a mean age of 39.64 ± 11.14 years (59.6% male). Participants completed questionnaires, including baseline information and psychological measurements, the SIS and Self-Rating Depression Scale. The psychometrics of the SIS and its association with depression were examined through exploratory factor analysis, confirmatory factor analysis and receiver operating characteristic analysis. RESULTS: The average participant SIS score was 42.66 ± 14.61 (range: 24-96) years. Analyses suggested the model had four factors: social rejection, financial insecurity, internalised shame and social isolation. The model fit statistics of the four-factor SIS were 0.913 for the comparative fit index, 0.902 for the Tucker-Lewis index and 0.088 for root-mean-square error of approximation. Standard estimated factor loadings ranged from 0.509 to 0.836. After controlling for demographic characteristics, the total score of the 23-item SIS predicted depression (odds ratio: 1.087, 95% CI 1.061-1.115; area under the curve: 0.84, 95% CI 0.788-0.892). CONCLUSIONS: The Chinese version of the SIS showed good psychometric properties and can be used to assess the level of perceived stigma experienced by asymptomatic COVID-19 carriers.

Lower-grade gliomas surgery guided by GRPR-targeting PET/NIR dual-modality image probe: a prospective and single-arm clinical trial.

Purpose: Lower-grade gliomas (LGGs) are a group of infiltrative growing glial brain tumors characterized by intricate intratumoral heterogeneity and subtle visual appearance differences from non-tumor tissue, which can lead to errors in pathologic tissue sampling. Although 5-ALA fluorescence has been an essential method for visualizing gliomas during surgery, its effectiveness is limited in the case of LGGs due to low sensitivity. Therefore, we developed a novel PET/NIR dual-modality image probe targeting gastrin-releasing peptide receptor (GRPR) in glioma cells to enhance tumor visualization and improve the accuracy of sampling. Methods: A prospective, non-randomized, single-center feasibility clinical trial (NCT03407781) was conducted in the referral center from October 21, 2016, to August 17, 2018. Consecutive enrollment included patients suspected of having LGGs and considered suitable candidates for surgical removal. Group 1 comprised ten patients who underwent preoperative 68Ga-IRDye800CW-BBN PET/MRI assessment followed by intraoperative fluorescence-guided surgery. Group 2 included 42 patients who underwent IRDye800CW-BBN fluorescence-guided surgery. The primary endpoints were the predictive value of preoperative PET imaging for intraoperative fluorescence and the sensitivity and specificity of fluorescence-guided sampling. Results: Thirty-nine patients were included in the in-depth analysis of endpoints, with 25 (64.1%) exhibiting visible fluorescence, while 14 (35.9%) did not. The preoperative positive PET uptake exhibited a greater accuracy in predicting intraoperative fluorescence compared to MRI enhancement (100% [10/10] vs. 87.2% [34/39]). A total of 125 samples were harvested during surgery. Compared with pathology, subjective fluorescence intensity showed a sensitivity of 88.6% and a specificity of 88.2% in identifying WHO grade III samples. For WHO grade II samples, the sensitivity and specificity of fluorescence were 54.7% and 88.2%, respectively. Conclusion: This study has demonstrated the feasibility of the novel dual-modality imaging technique for integrated pre- and intraoperative targeted imaging via the same molecular receptor in surgeries for LGGs. The PET/NIR dual-modality probe exhibits promise for preoperative surgical planning in fluorescence-guided surgery and provides greater accuracy in guiding tumor sampling compared to 5-ALA in patients with LGGs.

The value of 18F-FDG PET/CT in the systemic evaluation of patients with Rosai-Dorfman disease: a retrospective study and literature review.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare form of non-Langerhans cell histiocytic disease. The aim of this study was to review the characteristics of RDD using 18F-FDG PET/CT and determine its efficacy in the disease management. RESULTS: A total of 28 RDD patients underwent 33 18F-FDG PET/CT scans for systematic assessment and follow-up. The common involved sites included the lymph nodes (17, 60.7%), upper respiratory tract (11, 39.3%), and skin (9, 32.1%). Five patients had more lesions detected in PET/CT images than in CT and/or MRI, including inapparent nodules (n = 5) and bone destruction (n = 3). After thorough treatment evaluation using PET/CT, the treatment strategies of 14 patients (14/16, 87.5%) were changed. Five patients underwent PET/CT twice during follow-up and the SUVs were significantly decreased (15.3 ± 3.4 vs. 4.4 ± 1.0, p = 0.02), which demonstrated disease improvement. CONCLUSIONS: 18F-FDG PET/CT contributed to displaying the holistic characteristics of RDD, in particular during initial assessment, treatment strategy adjustment, or efficacy evaluation, and could compensate for some disadvantages of CT and MRI images.