Dual-Reference Source-Free Active Domain Adaptation for Nasopharyngeal Carcinoma Tumor Segmentation across Multiple Hospitals

Nasopharyngeal carcinoma (NPC) is a prevalent and clinically significant malignancy that predominantly impacts the head and neck area. Precise delineation of the Gross Tumor Volume (GTV) plays a pivotal role in ensuring effective radiotherapy for NPC. Despite recent methods that have achieved promising results on GTV segmentation, they are still limited by lacking carefully-annotated data and hard-to-access data from multiple hospitals in clinical practice. Although some unsupervised domain adaptation (UDA) has been proposed to alleviate this problem, unconditionally mapping the distribution distorts the underlying structural information, leading to inferior performance. To address this challenge, we devise a novel Sourece-Free Active Domain Adaptation (SFADA) framework to facilitate domain adaptation for the GTV segmentation task. Specifically, we design a dual reference strategy to select domain-invariant and domain-specific representative samples from a specific target domain for annotation and model fine-tuning without relying on source-domain data. Our approach not only ensures data privacy but also reduces the workload for oncologists as it just requires annotating a few representative samples from the target domain and does not need to access the source data. We collect a large-scale clinical dataset comprising 1057 NPC patients from five hospitals to validate our approach. Experimental results show that our method outperforms the UDA methods and achieves comparable results to the fully supervised upper bound, even with few annotations, highlighting the significant medical utility of our approach. In addition, there is no public dataset about multi-center NPC segmentation, we will release code and dataset for future research

The impact of canagliflozin on the risk of neuropathy events:A post-hoc exploratory analysis of the CREDENCE trial

Aim: Canagliflozin reduces the risk, and progression, of diabetic kidney disease. We hypothesized that it may improve the microvascular complication of neuropathy. Methods: The CREDENCE trial randomized participants with type 2 diabetes and kidney disease to canagliflozin 100 mg daily or placebo. Neuropathy events were defined post-hoc as any reported adverse event consistent with a peripheral or autonomic neuropathy event. The effect of canagliflozin and predictors of neuropathy events were estimated using Cox regression analysis. In sensitivity analyses the endpoint was restricted to sensorimotor polyneuropathy, diabetic neuropathy, and non-autonomic neuropathy events. Results: Almost half (48.8%) of the 4401 participants had a diagnosis of neuropathy at baseline. Over a median of 2.45 years of follow up, 657 people experienced a neuropathy event (63.2 per 1000 patient-years). Independent factors associated with higher risk of experiencing neuropathy events were non-white race, younger age, higher glycated haemoglobin and lower estimated glomerular filtration rate. The incidence of neuropathy events was similar in people randomized to canagliflozin and placebo (334/2202 vs. 323/2199; HR 1.04, 95% CI 0.89 to 1.21, P = 0.66). Canagliflozin had no impact on sensorimotor polyneuropathy (HR 0.93, 95% CI 0.69 to 1.25, P = 0.63), diabetic neuropathy (HR 0.91, 95% CI 0.68 to 1.22, P = 0.52), or non-autonomic neuropathy (HR 1.03, 95% CI 0.87 to 1.21, P = 0.77). The lack of effect on neuropathy events was consistent in subgroup analyses. Conclusion: Canagliflozin did not affect the risk of neuropathy events in the CREDENCE trial. Future large randomized studies with prespecified neuropathy endpoints are required to determine the impact of sodium glucose cotransporter 2 inhibitors on diabetic neuropathy

Effects of Discarded Masks on the Offshore Microorganisms during the COVID-19 Pandemic

Numerous disposable plastic masks had been produced and used for preventing the worldwide COVID-19 pandemic effectively. Discarded masks are a potential source of microplastic pollution in marine ecosystems. The effect of discarded masks on offshore microorganisms is still unclear. Herein, we profiled the interaction between the microplastics released by discarded masks and marine microbes. The effects of mask quantity, time, and environment on the microplastic-related communities were determined. We characterized the bacterial communities of each group using 16S rRNA gene sequencing and metagenomic sequencing and correlated the community diversity to the physicochemical properties of seawater. We found that the diversity and richness of microflora on the surface of microplastics with different quantity and time varied significantly. Proteobacteria are the main bacteria on microplastics, and the KEGG metabolic pathway prediction shows that amino acid metabolism and carbohydrate metabolism were abundant. In addition, there was a correlation between bacterial communities and Antibiotic Resistance Ontology (ARO). We used scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR) techniques to evaluate the plastic polymer characteristics of disposable medical masks. Our research shows that disposable medical masks immersed in seawater can alter the microbial community. This study provides the most recent data and insights into the contamination of discarded masks in the marine environment

Long‐term outcomes of metastasis‐directed stereotactic body radiation therapy in metastatic nasopharyngeal carcinoma

Abstract Background The study aims to evaluate the outcomes of metastasis‐directed stereotactic body radiation therapy (SBRT) in metastatic nasopharyngeal carcinoma (mNPC). Methods We reviewed all SBRT conducted in patients with mNPC in our institution between 2013 and 2022. Systemic therapy was performed with chemotherapy with or without anti‐programmed death‐1 (PD‐1) therapy. Local treatment delivered with ablative purpose in stereotactic setting with dose/fraction ≥5 Gy was evaluated. Kaplan–Meier analyses were used to determine the rates of local control (LC), progression‐free survival (PFS), and overall survival (OS). Univariate and multivariate analyses were performed by Cox regression. Results A total of 54 patients with 76 metastatic sites receiving SBRT were analyzed. Median follow‐up was 49 months. The 3‐year LC, PFS, and OS rates were 89.1%, 29.4%, and 57.9%, respectively. Adding a PD‐1 inhibitor to SBRT tended to prolong median OS (50.1 vs. 32.2 months, p = 0.068). Patients receiving a biological effective dose (BED, α/β = 10) ≥ 80 Gy had a significantly longer median OS compared to those who received a lower dose (not reached vs. 29.5 months, p = 0.004). Patients with oligometastases (1–5 metastases) had a better median OS (not reached vs. 29.5 months, p < 0.001) and PFS (34.3 vs. 4.6 months, p < 0.001). Pretreatment EBV‐DNA and maintenance therapy were also significant predictors for OS. Conclusions Metastatic NPC patients could benefit from metastases‐directed SBRT in combination with systemic therapy

Retinopathy is associated with impaired cognition in patients undergoing peritoneal dialysis

AbstractObjective: Previous studies have shown a relationship between retinopathy and cognition including population with and without chronic kidney disease (CKD) but data regarding peritoneal dialysis (PD) are limited. This study aims to investigate the relationship between retinopathy and cognitive impairment in patients undergoing peritoneal dialysis (PD). Methods: In this observational study, we recruited a total of 107 participants undergoing PD, consisting of 48 men and 59 women, ages ranging from 21 to 78 years. The study followed a cross-sectional design. Retinal microvascular characteristics, such as geometric changes in retinal vascular including tortuosity, fractal dimension (FD), and calibers, were assessed. Retinopathy (such as retinal hemorrhage or microaneurysms) was evaluated using digitized photographs. The Modified Mini-Mental State Examination (3MS) was performed to assess global cognitive function. Results: The prevalence rates of retinal hemorrhage, microaneurysms, and retinopathy were 25%, 30%, and 43%, respectively. The mean arteriolar and venular calibers were 63.2 and 78.5 µm, respectively, and the corresponding mean tortuosity was 37.7 ± 3.6 and 37.2 ± 3.0 mm−1. The mean FD was 1.49. After adjusting for age, sex, education, mean arterial pressure, and Charlson index, a negative association was revealed between retinopathy and 3MS scores (regression coefficient: −3.71, 95% confidence interval: −7.09 to −0.33, p = 0.03). Conclusions: Retinopathy, a condition common in patients undergoing PD, was associated with global cognitive impairment. These findings highlight retinopathy, can serve as a valuable primary screening tool for assessing the risk of cognitive decline

Recent Advances of Organ-on-a-Chip in Cancer Modeling Research

Although many studies have focused on oncology and therapeutics in cancer, cancer remains one of the leading causes of death worldwide. Due to the unclear molecular mechanism and complex in vivo microenvironment of tumors, it is challenging to reveal the nature of cancer and develop effective therapeutics. Therefore, the development of new methods to explore the role of heterogeneous TME in individual patients’ cancer drug response is urgently needed and critical for the effective therapeutic management of cancer. The organ-on-chip (OoC) platform, which integrates the technology of 3D cell culture, tissue engineering, and microfluidics, is emerging as a new method to simulate the critical structures of the in vivo tumor microenvironment and functional characteristics. It overcomes the failure of traditional 2D/3D cell culture models and preclinical animal models to completely replicate the complex TME of human tumors. As a brand-new technology, OoC is of great significance for the realization of personalized treatment and the development of new drugs. This review discusses the recent advances of OoC in cancer biology studies. It focuses on the design principles of OoC devices and associated applications in cancer modeling. The challenges for the future development of this field are also summarized in this review. This review displays the broad applications of OoC technique and has reference value for oncology development

Autocrine parathyroid hormone-like hormone promotes intrahepatic cholangiocarcinoma cell proliferation via increased ERK/JNK-ATF2-cyclinD1 signaling

Abstract Background and aims Intrahepatic cholangiocarcinoma (ICC) is an aggressive tumor with a high fatality rate. It was recently found that parathyroid hormone-like hormone (PTHLH) was frequently overexpressed in ICC compared with non-tumor tissue. This study aimed to elucidate the underlying mechanisms of PTHLH in ICC development. Methods The CCK-8 assay, colony formation assays, flow cytometry and a xenograft model were used to examine the role of PTHLH in ICC cells proliferation. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins. Luciferase reporter, chromatin immunoprecipitation (ChIP) and DNA pull-down assays were used to verify the transcription regulation of activating transcription factor-2 (ATF2). Results PTHLH was significantly upregulated in ICC compared with adjacent and normal tissues. Upregulation of PTHLH indicated a poor pathological differentiation and intrahepatic metastasis. Functional study demonstrated that PTHLH silencing markedly suppressed ICC cells growth, while specific overexpression of PTHLH has the opposite effect. Mechanistically, secreted PTHLH could promote ICC cell growth by activating extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and subsequently upregulated ATF2 and cyclinD1 expression. Further study found that the promoter activity of PTHLH were negatively regulated by ATF2, indicating that a negative feedback loop exists. Conclusions Our findings demonstrated that the ICC-secreted PTHLH plays a characteristic growth-promoting role through activating the canonical ERK/JNK-ATF2-cyclinD1 signaling pathways in ICC development. We identified a negative feedback loop formed by ATF2 and PTHLH. In this study, we explored the therapeutic implication for ICC patients

Rational Hydrogenation for Enhanced Mobility and High Reliability on ZnO-based Thin Film Transistors: From Simulation to Experiment

Hydrogenation is one of the effective methods for improving the performance of ZnO thin film transistors (TFTs), which originate from the fact that hydrogen (H) acts as a defect passivator and a shallow <i>n</i>-type dopant in ZnO materials. However, passivation accompanied by an excessive H doping of the channel region of a ZnO TFT is undesirable because high carrier density leads to negative threshold voltages. Herein, we report that Mg/H codoping could overcome the trade-off between performance and reliability in the ZnO TFTs. The theoretical calculation suggests that the incorporation of Mg in hydrogenated ZnO decrease the formation energy of interstitial H and increase formation energy of O-vacancy (<i>V</i>_O). The experimental results demonstrate that the existence of the diluted Mg in hydrogenated ZnO TFTs could be sufficient to boost up mobility from 10 to 32.2 cm²/(V s) at a low carrier density (∼2.0 × 10¹⁸ cm^–3), which can be attributed to the decreased electron effective mass by surface band bending. The all results verified that the Mg/H codoping can significantly passivate the <i>V</i>_O to improve device reliability and enhance mobility. Thus, this finding clearly points the way to realize high-performance metal oxide TFTs for low-cost, large-volume, flexible electronics

High-Temperature Ferroelectricity and Photoluminescence in a Hybrid Organic–Inorganic Compound: (3-Pyrrolinium)MnCl₃

Coupling of ferroelectricity and optical properties has become an interesting aspect of material research. The switchable spontaneous polarization in ferroelectrics provides an alternative way to manipulate the light–matter interaction. The recent observation of strong photoluminescence emission in ferroelectric hybrid organic–inorganic compounds, (pyrrolidinium)­MnX₃ (X = Cl or Br), is an attractive approach to high efficiency luminescence with the advantages of ferroelectricity. However, (pyrrolidinium)­MnX₃ only displays ferroelectricity near or below room temperature, which limits its future applications in optoelectronics and multifunctional devices. Here, we rationally designed and synthesized high-temperature luminescent ferroelectric materials. The new hybrid compound (3-pyrrolinium)­MnCl₃ has a very high Curie temperature, <i>T</i>_c = 376 K, large spontaneous electronic polarization of 6.2 μC/cm², and high fatigue resistance, as well as high emission efficiency of 28%. This finding is a further step to the practical use of ferroelectric luminescence based on organic–inorganic compounds