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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). [ABSTRACT FROM AUTHOR]

Purpose: Drug use is quite common in transgender women, but the mechanisms of the drug use remain unclear. The purpose of this study was to investigate the mediating role of loneliness in perceived stress and the drug use among transgender women. Methods: A cross-sectional survey was conducted from April to September 2018 in Shenyang and Kunming, China, among 247 transgender women. Chinese Perceived Stress Scale, the Chinese version of 8-item UCLA Loneliness Scale, a drug use questionnaire, and a demographic characteristic questionnaire were included in the survey. Descriptive analysis, logistic regression, and mediation analysis were done using SPSS Statistics version 26.0 and Mplus version 8.3. Results: The mean age of transgender women in the study was 33.04 years (standard deviation=8.14). Around 33.20% (n=82) of transgender women reported ever using one kind of drugs, the most commonly used drugs were rush (79.20%), ice (8.50%), and 5-MeO-DIPT (8.50%). Univariate logistic regression showed that perceived stress (odds ratio [OR]=1.73, 95% bootstrap confidence intervals [CI]=1.27–2.36) and loneliness (OR=1.62, 95% CI=1.23–2.13) had a significant association with drug use, all p [ps] <0.01. The effect of perceived stress on drug use was partially mediated by feeling of loneliness (estimate=0.09, standard error=0.04, p<0.05), the mediating effect (0.09) accounted for 27.27% of the total effect (0.33). Conclusion: Perceived stress can positively predict drug use. Loneliness plays an important role in drug use among transgender women. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Mapping wall-to-wall forest aboveground biomass (AGB) at large scales is critical for understanding global climate change and the carbon cycle. In previous studies, a regression-based method was commonly used to map the spatially continuous distribution of forest AGB with the aid of optical images, which may suffer from the saturation effect. The Global Ecosystem Dynamics Investigation (GEDI) can collect forest vertical structure information with high precision on a global scale. In this study, we proposed a collaborative kriging (co-kriging) interpolation-based method for mapping spatially continuous forest AGB by integrating GEDI and Sentinel-2 data. First, by fusing spectral features from Sentinel-2 images with vertical structure features from GEDI, the optimal estimation model for footprint-level AGB was determined by comparing different machine-learning algorithms. Second, footprint-level predicted AGB was used as the main variable, with rh95 and B12 as covariates, to build a co-kriging guided interpolation model. Finally, the interpolation model was employed to map wall-to-wall forest AGB. The results showed the following: (1) For footprint-level AGB, CatBoost achieved the highest accuracy by fusing features from GEDI and Sentinel-2 data ( R 2 = 0.87, RMSE = 49.56 Mg/ha, rRMSE = 27.06%). (2) The mapping results based on the interpolation method exhibited relatively high accuracy and mitigated the saturation effect in areas with higher forest AGB ( R 2 = 0.69, RMSE = 81.56 Mg/ha, rRMSE = 40.98%, bias = −3.236 Mg/ha). The mapping result demonstrates that the proposed method based on interpolation combined with multi-source data can be a promising solution for monitoring spatially continuous forest AGB. [ABSTRACT FROM AUTHOR]

Vegetation plays a crucial role in terrestrial ecosystems, and the FVC (Fractional Vegetation Coverage) is a key indicator reflecting the growth status of vegetation. The accurate quantification of FVC dynamics and underlying driving factors has become a hot topic. However, the scale effect on FVC changes and driving factors has received less attention in previous studies. In this study, the changes and driving factors of FVC at multiple scales were analyzed to reveal the spatial and temporal change in vegetation in the Henan section of the Yellow River basin. Firstly, based on the pixel dichotomy model, the FVC at different times and spatial scales was calculated using Landsat-8 data. Then, the characteristics of spatial and temporal FVC changes were analyzed using simple linear regression and CV (Coefficient of Variation). Finally, a GD (Geographic Detector) was used to quantitatively analyze the driving factors of FVC at different scales. The results of this study revealed that (1) FVC showed an upward trend at all spatial scales, increasing by an average of 0.55% yr−1 from 2014 to 2022. The areas with an increasing trend in FVC were 10.83% more than those with a decreasing trend. (2) As the spatial scale decreased, the explanatory power of the topography factors (aspect, elevation, and slope) for changes in FVC was gradually strengthened, while the explanatory power of climate factors (evapotranspiration, temperature, and rainfall) and anthropogenic activities (night light) for changes in FVC decreased. (3) The q value of evapotranspiration was always the highest across different scales, peaking notably at a spatial scale of 1000 m (q = 0.48). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Integrin receptor αvβ3 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. [ABSTRACT FROM AUTHOR]

Purpose: Although transgender women (TGW) bear the highest HIV burden worldwide, routine surveillance of this group is rare. We aimed to evaluate the trends in health characteristics of Chinese TGW. Methods: Three cross-sectional studies using snowball sampling were conducted in 2014, 2017, and 2019, primarily in Shenyang, China. A questionnaire and voluntary HIV testing were used to obtain information on background characteristics, sexual behaviors, pre-exposure prophylaxis (PrEP) willingness, and HIV status. Results: There were 220 respondents in 2014, 198 in 2017, and 247 in 2019 (average age 31.1±7.6 to 33.5±9.6 years). HIV prevalence significantly decreased from 29.5% (95% confidence interval [CI]: 25.3–38.4%) in 2014 to 19.4% (95% CI: 14.7–24.9%) in 2019 (p<0.05). The proportion of participants reporting condomless anal intercourse (CAI) with any partner fluctuated from 30.8% (95% CI: 25.1–36.1%) to 53.0% (95% CI: 45.8–60.1%). The proportion of participants willing to use PrEP decreased from 86.4% (95% CI: 81.1–90.6%) in 2014 to 62.8% (95% CI: 56.4–68.8%) in 2019. Factors significantly associated with HIV infection were CAI with any partner (multivariate odds ratio [ORm]: 3.58, 95% CI: 1.55–8.29 in 2017; ORm: 3.18, 95% CI: 1.56–6.46 in 2019) and PrEP willingness (ORm: 0.26, 95% CI: 0.12–0.58 in 2017). Conclusion: HIV prevalence and associated risk factors remain substantial among Chinese TGW. There is an urgent need to strengthen HIV surveillance in this population, and develop trans-friendly and effective interventions to minimize HIV prevalence and transmission. [ABSTRACT FROM AUTHOR]

Purpose: High prevalence of depression in transgender women highlights the importance of validating the measure to assess depression. Moreover, depression is significantly associated with suicide across research studies. The aims of the current study were to validate a Chinese-language version of the Patient Health Questionnaire-9 (PHQ-9) and to assess operating characteristics of the PHQ-9 for suicide screening in transgender women. Methods: With the approval of an Institutional Review Board (IRB), a total of 198 transgender women living in Shenyang, China, were recruited, and asked to complete the PHQ-9, including measures of their suicidal ideation, planning and attempt. Results: A one-factor model of the PHQ-9 was supported in the current sample, showing good reliability and validity. The best cutoff point for the PHQ-9 in suicidal ideation was 17, with a sensitivity/specificity of 77.78%; the best cutoff point for PHQ-9 in suicidal planning was 17, with a sensitivity of 81.82% and a specificity of 73.26%; and the best cutoff point for PHQ-9 in suicidal attempt was 20, with a sensitivity of 75% and a specificity of 90.21%. Conclusion: Findings supported the validity of the PHQ-9. With potential clinical or research application, the PHQ-9 can be an efficient instrument for suicide screening in transgender women. [ABSTRACT FROM AUTHOR]