The GFPT2-O-GlcNAcylation-YBX1 axis promotes IL-18 secretion to regulate the tumor immune microenvironment in pancreatic cancer.

The immunosuppressive microenvironment caused by several intrinsic and extrinsic mechanism has brought great challenges to the immunotherapy of pancreatic cancer. We identified GFPT2, the key enzyme in hexosamine biosynthesis pathway (HBP), as an immune-related prognostic gene in pancreatic cancer using transcriptome sequencing and further confirmed that GFPT2 promoted macrophage M2 polarization and malignant phenotype of pancreatic cancer. HBP is a glucose metabolism pathway leading to the generation of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), which is further utilized for protein O-GlcNAcylation. We confirmed GFPT2-mediated O-GlcNAcylation played an important role in regulating immune microenvironment. Through cellular proteomics, we identified IL-18 as a key downstream of GFPT2 in regulating the immune microenvironment. Through CO-IP and protein mass spectrum, we confirmed that YBX1 was O-GlcNAcylated and nuclear translocated by GFPT2-mediated O-GlcNAcylation. Then, YBX1 functioned as a transcription factor to promote IL-18 transcription. Our study elucidated the relationship between the metabolic pathway of HBP in cancer cells and the immune microenvironment, which might provide some insights into the combination therapy of HBP vulnerability and immunotherapy in pancreatic cancer.

Posterior eye delivery of angiogenesis-inhibiting RNA nanoparticles via subconjunctival injection.

Neovascularization contributes to various posterior eye segment diseases such as age-related macular degeneration and diabetic retinopathy. RNA nanoparticles were demonstrated previously to enter the corneal and retinal cells after subconjunctival injection for ocular delivery. In the present study, antiangiogenic aptamers (anti-vascular endothelial growth factor (VEGF) and anti-angiopoietin-2 (Ang2) aptamers) were conjugated to RNA nanoparticles. The objectives were to investigate the clearance and distribution of these angiogenesis-inhibiting RNA nanoparticles after subconjunctival injection in vivo and their antiangiogenic effects for inhibiting ocular neovascularization in vitro. The results in the whole-body fluorescence imaging study showed that the clearance of RNA nanoparticles was size-dependent with no significant differences between RNA nanoparticles with and without the aptamers except for pRNA-3WJ. The distribution study of RNA nanoparticles by confocal microscopy of the dissected eye tissues in vivo indicated cell internalization of the larger RNA nanoparticles in the retina and retinal pigment epithelium after subconjunctival injection, and the larger nanoparticles with aptamers showed higher levels of cell internalization than those without. In the cell proliferation assay in vitro, RNA nanoparticles with multiple aptamers had higher antiangiogenic effects. With both longer retention time and high antiangiogenic effect, SQR-VEGF-Ang2 could be a promising RNA nanoparticle for posterior eye delivery.

Association between dietary inflammation index and cataract: a population-based study from NHANES 2005-2008.

Importance: Various studies have widely explored the association between index of dietary inflammation (DII) and occurrence of diseases. Accumulating evidence have revealed that a lower DII seems to be protective against a variety of diseases. Nevertheless, the association between DII and age-related cataract remains unclear. Objective: To investigate the correlation between DII and age-related cataract in a representative sample of the American population. Design setting and participants: This cross-sectional population-based study comprised 6,395 participants from the National Health and Nutrition Examination Survey (NHANES) conducted in cycles from 2005 to 2008. DII was calculated using dietary recall information, with higher scores indicating greater inflammatory potential of the diet. Age-related cataract was evaluated using cataract surgery as a surrogate measure. Covariates included sociodemographic factors, lifestyle factors, physical measures, and comorbidities. Logistic regression models were employed to assess the association between DII and cataract. The presence of a non-linear relationship was examined using restricted cubic spline analysis. Subgroup analysis was conducted to explore potential interaction effects. Data analysis was performed from September 1 to December 30, 2022. Main outcomes and measures: Age-related cataract assessed through cataract surgery information obtained from a self-reported questionnaire. Results: A total of 6,395 participants were included, with a mean (standard deviation, SD) age of 48.7 (15.3) years. Of these, 3,115 (48.7%) were male, 3,333 (52.1%) were non-Hispanic white, and 683 (10.7%) had cataract. The mean (SD) DII was -4.78 (1.74). After adjusting for all included covariates, DII showed a positive association with cataract, both as a continuous variable (odds ratio (OR): 1.054, 95% confidence interval (CI): 1.007-1.103, p = 0.023) and in quartiles, with the highest quartile compared to the lowest (OR: 1.555, 95% CI: 1.233-1.967, p < 0.001). Restricted cubic spline analysis revealed no evidence of a non-linear relationship (p for non-linearity 0.085). Subgroup analysis indicated no interaction effects among the studied covariates. Conclusions and relevance: These findings suggest that a pro-inflammatory diet serves as a risk factor for the occurrence of cataracts.

Salvage Surgery for Initially Unresectable HCC With PVTT Converted by Locoregional Treatment Plus Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody.

BACKGROUND: This study aimed to compare the survival outcomes of patients with initially unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) who underwent or did not undergo salvage surgery followed by a triple combination conversion treatment consisted of locoregional treatment (LRT), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies. METHODS: The data from 93 consecutive patients with initially unresectable HCC and PVTT across 4 medical centers were retrospectively reviewed. They were converted successfully by the triple combination treatment and underwent or did not undergo salvage resection. The baseline characteristics, conversion schemes, conversion treatment-related adverse events (CTRAEs), overall survival (OS), and progression-free survival (PFS) of the salvage surgery and non-surgery groups were compared. Multivariate Cox regression analysis was performed to identify independent risk factors for OS and PFS. Additionally, subgroup survival analysis was conducted by stratification of degree of tumor response and type of PVTT. RESULTS: Of the 93 patients, 44 underwent salvage surgery, and 49 did not undergo salvage surgery. The OS and PFS of the salvage surgery and non-surgery groups were not significantly different (P = .370 and .334, respectively). The incidence and severity of CTRAEs of the 2 groups were also comparable. Subgroup analyses revealed that for patients with complete response (CR) or types III-IV PVTT, there was a trend toward better survival in patients who did not undergo salvage surgery. Multivariate analysis showed that baseline α-fetoprotein and best tumor response per mRECIST criteria were independent prognostic factors for OS and PFS. CONCLUSIONS: For patients with initially unresectable HCC and PVTT who were successfully converted by the triple combination therapy, salvage liver resection may not be necessary, especially for the patients with CR or types III-IV PVTT.

lncCPSET1 acts as a scaffold for MLL2/COMPASS to regulate Bmp4 and promote the formation of chicken primordial germ cells.

Primordial germ cells (PGCs) are the ancestors of female and male germ cells. Recent studies have shown that long non-coding RNA (lncRNA) and histone methylation are key epigenetic factors affecting PGC formation; however, their joint regulatory mechanisms have rarely been studied. Here, we explored the mechanism by which lncCPSET1 and H3K4me2 synergistically regulate the formation of chicken PGCs for the first time. Combined with chromatin immunoprecipitation (CHIP) sequencing and RNA-seq of PGCs transfected with the lncCPSET1 overexpression vector, GO annotation and KEGG enrichment analysis revealed that Wnt and TGF-ß signaling pathways were significantly enriched, and Fzd2, Id1, Id4, and Bmp4 were identified as candidate genes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that ASH2L, DPY30, WDR5, and RBBP5 overexpression significantly increased the expression of Bmp4, which was up-regulated after lncCPSET1 overexpression as well. It indicated that Bmp4 is a target gene co-regulated by lncCPSET1 and MLL2/COMPASS. Interestingly, co-immunoprecipitation results showed that ASH2L, DPY30 and WDR5 combined and RBBP5 weakly combined with DPY30 and WDR5. lncCPSET1 overexpression significantly increased Dpy30 expression and co-immunoprecipitation showed that interference/overexpression of lncCPSET1 did not affect the binding between the proteins in the complexes, but interference with lncCPSET1 inhibited DPY30 expression, which was confirmed by RNA immunoprecipitation that lncCPSET1 binds to DPY30. Additionally, CHIP-qPCR results showed that DPY30 enriched in the Bmp4 promoter region promoted its transcription, thus promoting the formation of PGCs. This study demonstrated that lncCPSET1 and H3K4me2 synergistically promote PGC formation, providing a reference for the study of the regulatory mechanisms between lncRNA and histone methylation, as well as a molecular basis for elucidating the formation mechanism of PGCs in chickens.

Towards overcoming obstacles of type II photodynamic therapy: Endogenous production of light, photosensitizer, and oxygen.

Conventional photodynamic therapy (PDT) approaches face challenges including limited light penetration, low uptake of photosensitizers by tumors, and lack of oxygen in tumor microenvironments. One promising solution is to internally generate light, photosensitizers, and oxygen. This can be accomplished through endogenous production, such as using bioluminescence as an endogenous light source, synthesizing genetically encodable photosensitizers in situ, and modifying cells genetically to express catalase enzymes. Furthermore, these strategies have been reinforced by the recent rapid advancements in synthetic biology. In this review, we summarize and discuss the approaches to overcome PDT obstacles by means of endogenous production of excitation light, photosensitizers, and oxygen. We envision that as synthetic biology advances, genetically engineered cells could act as precise and targeted "living factories" to produce PDT components, leading to enhanced performance of PDT.

Toxicokinetics of MDMA and Its Metabolite MDA in Rats.

OBJECTIVES: To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine (MDMA) and its metabolite 4,5-methylene dioxy amphetamine (MDA) in rats after single and continuous administration of MDMA, providing reference data for the forensic identification of MDMA. METHODS: A total of 24 rats in the single administration group were randomly divided into 5, 10 and 20 mg/kg experimental groups and the control group, with 6 rats in each group. The experimental group was given intraperitoneal injection of MDMA, and the control group was given intraperitoneal injection of the same volume of normal saline as the experimental group. The amount of 0.5 mL blood was collected from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. In the continuous administration group, 24 rats were randomly divided into the experimental group (18 rats) and the control group (6 rats). The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5, 7, 9, 11, 13, 15, 17 mg/kg per day, respectively, while the control group was given the same volume of normal saline as the experimental group by intraperitoneal injection. On the eighth day, the experimental rats were randomly divided into 5, 10 and 20 mg/kg dose groups, with 6 rats in each group. MDMA was injected intraperitoneally, and the control group was injected intraperitoneally with the same volume of normal saline as the experimental group. On the eighth day, 0.5 mL of blood was taken from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels, and statistical software was employed for data analysis. RESULTS: In the single-administration group, peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration, respectively, with the largest detection time limit of 12 h. In the continuous administration group, peak concentrations were reached at 30 min and 1.5 h after administration, respectively, with the largest detection time limit of 10 h. Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows: T=10.362C-1.183, R2=0.974 6; T=7.397 3C-0.694, R2=0.961 5 (T: injection time; C: concentration ratio of MDMA to MDA in plasma). CONCLUSIONS: The toxicokinetic data of MDMA and its metabolite MDA in rats, obtained through single and continuous administration, including peak concentration, peak time, detection time limit, and the relationship between concentration ratio and administration time, provide a theoretical and data foundation for relevant forensic identification.

A systematic review of economic evaluation of artificial intelligence-based screening for eye diseases: From possibility to reality.

Artificial Intelligence (AI) has become a focus of research in the rapidly evolving field of ophthalmology. Nevertheless, there is a lack of systematic studies on the health economics of AI in this field. We examine studies from the PubMed, Google Scholar, and Web of Science databases that employed quantitative analysis, retrieved up to July 2023. Most of the studies indicate that AI leads to cost savings and improved efficiency in ophthalmology. On the other hand, some studies suggest that using AI in healthcare may raise costs for patients, especially when taking into account factors such as labor costs, infrastructure, and patient adherence. Future research should cover a wider range of ophthalmic diseases beyond common eye conditions. Moreover, conducting extensive health economic research, designed to collect data relevant to its own context, is imperative.

PGKD-Net: Prior-guided and Knowledge Diffusive Network for Choroid Segmentation.

The thickness of the choroid is considered to be an important indicator of clinical diagnosis. Therefore, accurate choroid segmentation in retinal OCT images is crucial for monitoring various ophthalmic diseases. However, this is still challenging due to the blurry boundaries and interference from other lesions. To address these issues, we propose a novel prior-guided and knowledge diffusive network (PGKD-Net) to fully utilize retinal structural information to highlight choroidal region features and boost segmentation performance. Specifically, it is composed of two parts: a Prior-mask Guided Network (PG-Net) for coarse segmentation and a Knowledge Diffusive Network (KD-Net) for fine segmentation. In addition, we design two novel feature enhancement modules, Multi-Scale Context Aggregation (MSCA) and Multi-Level Feature Fusion (MLFF). The MSCA module captures the long-distance dependencies between features from different receptive fields and improves the model's ability to learn global context. The MLFF module integrates the cascaded context knowledge learned from PG-Net to benefit fine-level segmentation. Comprehensive experiments are conducted to evaluate the performance of the proposed PGKD-Net. Experimental results show that our proposed method achieves superior segmentation accuracy over other state-of-the-art methods. Our code is made up publicly available at: https://github.com/yzh-hdu/choroid-segmentation.

Polar coordinate active-matrix digital microfluidics for high-resolution concentration gradient generation.

Automated concentration gradient generation is one of the most important applications of lab-on-a-chip devices. Digital microfluidics is a unique platform that can effectively achieve digitalized gradient concentration preparation. However, the dynamic range and concentration resolution of the prepared samples heavily rely on the size and the number of effective electrodes. In this work, we report an active-matrix digital microfluidic device with polar coordinate electrode arrangement. The device contains 33 different electrode sizes, generating digital droplets of different volumes. To compare with the conventional rectangular coordinate arrangement with a similar electrode number, this work shows an approximately 19 times resolution enhancement for the achievable concentration gradient. We characterized the stability and uniformity of droplets generated by electrodes of different sizes, and the coefficient of variation of stable droplets was less than 3%. The fluorescent nanomaterial's concentration quantification and glucose concentration characterization experiments were also conducted, and the correlation coefficients for the linearities were all above 0.99.

BZW2 promotes malignant progression in lung adenocarcinoma through enhancing the ubiquitination and degradation of GSK3ß.

The role of Basic leucine zipper and W2 domains 2 (BZW2) in the advancement of different types of tumors is noteworthy, but its involvement and molecular mechanisms in lung adenocarcinoma (LUAD) remain uncertain. Through this investigation, it was found that the upregulation of BZW2 was observed in LUAD tissues, which was associated with an unfavorable prognosis for individuals diagnosed with LUAD, as indicated by data from Gene Expression Omnibus and The Cancer Genome Atlas databases. Based on the clinicopathologic characteristics of LUAD patients from the tissue microarray, both univariate and multivariate analyses indicated that BZW2 functioned as an independent prognostic factor for LUAD. In terms of mechanism, BZW2 interacted with glycogen synthase kinase-3 beta (GSK3ß) and enhanced the ubiquitination-mediated degradation of GSK3ß through slowing down of the dissociation of the ubiquitin ligase complex, which consists of GSK3ß and TNF receptor-associated factor 6. Moreover, BZW2 stimulated Wnt/ß-catenin signaling pathway through GSK3ß, thereby facilitating the advancement of LUAD. In conclusion, BZW2 was a significant promoter of LUAD. The research we conducted identified a promising diagnostic and therapeutic target for LUAD.

In vitro fermentation characteristics of polysaccharides from coix seed and its effects on the gut microbiota.

Coix seed polysaccharides had received increasing attention due to their diverse biological activities. In this study, a homogeneous polysaccharide (CSPW) was extracted and purified from coix seed. Furthermore, the saliva-gastrointestinal digestion and fecal fermentation behavior of CSPW were simulated in vitro. The results showed that CSPW was mainly composed of glucose. It cannot be degraded by the simulated salivary and intestinal digestive system, but can be degraded by the simulated gastric digestive system. After fermentation for 24 h, CSPW promoted the production of short-chain fatty acids (SCFAs), with acetic acid, propionic acid and n-butyric acid being the main metabolites. In addition, CSPW could significantly regulate the composition and microbial diversity of gut microbiota by increasing the relative abundance of beneficial bacteria, such as Limosilicactobacillus, Bifidobacterium and Collinsella. Finally, further analysis of functional prediction revealed that amino acid metabolism, nucleotide metabolism and carbohydrate metabolism were the most important pathways for CSPW to promote health. In summary, our findings suggested that CSPW could potentially be used as a good source of prebiotics because it can be used by gut microbiota to produce SCFAs and regulate the gut microbiota.

Segmentation of Low-Light Optical Coherence Tomography Angiography Images under the Constraints of Vascular Network Topology.

Optical coherence tomography angiography (OCTA) offers critical insights into the retinal vascular system, yet its full potential is hindered by challenges in precise image segmentation. Current methodologies struggle with imaging artifacts and clarity issues, particularly under low-light conditions and when using various high-speed CMOS sensors. These challenges are particularly pronounced when diagnosing and classifying diseases such as branch vein occlusion (BVO). To address these issues, we have developed a novel network based on topological structure generation, which transitions from superficial to deep retinal layers to enhance OCTA segmentation accuracy. Our approach not only demonstrates improved performance through qualitative visual comparisons and quantitative metric analyses but also effectively mitigates artifacts caused by low-light OCTA, resulting in reduced noise and enhanced clarity of the images. Furthermore, our system introduces a structured methodology for classifying BVO diseases, bridging a critical gap in this field. The primary aim of these advancements is to elevate the quality of OCTA images and bolster the reliability of their segmentation. Initial evaluations suggest that our method holds promise for establishing robust, fine-grained standards in OCTA vascular segmentation and analysis.

Real-Time Quantification of Nanoplastics-Induced Oxidative Stress in Stretching Alveolar Cells.

Nanoplastics from air pollutants can be directly inhaled into the alveoli in the lungs and further enter blood circulation, and numerous studies have revealed the close relation between internalized nanoplastics with many physiological disorders via intracellular oxidative stress. However, the dynamic process of nanoplastics-induced oxidative stress in lung cells under breath-mimicked conditions is still unclear, due to the lack of methods that can reproduce the mechanical stretching of the alveolar and simultaneously monitor the oxidative stress response. Here, we describe a biomimetic platform by culturing alveoli epithelial cells on a stretchable electrochemical sensor and integrating them into a microfluidic device. This allows reproducing the respiration of alveoli by cyclic stretching of the alveoli epithelial cells and monitoring the nanoplastics-induced oxidative stress by the built-in sensor. By this device, we prove that cyclic stretches can greatly enhance the cellular uptake of nanoplastics with the dependencies of strain amplitude. Importantly, oxidative stress evoked by internalized nanoplastics can be quantitatively monitored in real time. This work will promote the deep understanding about the cytotoxicity of inhaled nanoplastics in the pulmonary mechanical microenvironment.

In Vitro and In Vivo Evaluation of the Pathology and Safety Aspects of Three- and Four-Way Junction RNA Nanoparticles.

RNA therapeutics has advanced into the third milestone in pharmaceutical drug development, following chemical and protein therapeutics. RNA itself can serve as therapeutics, carriers, regulators, or substrates in drug development. Due to RNA's motile, dynamic, and deformable properties, RNA nanoparticles have demonstrated spontaneous targeting and accumulation in cancer vasculature and fast excretion through the kidney glomerulus to urine to prevent possible interactions with healthy organs. Furthermore, the negatively charged phosphate backbone of RNA results in general repulsion from negatively charged lipid cell membranes for further avoidance of vital organs. Thus, RNA nanoparticles can spontaneously enrich tumor vasculature and efficiently enter tumor cells via specific targeting, while those not entering the tumor tissue will clear from the body quickly. These favorable parameters have led to the expectation that RNA has low or little toxicity. RNA nanoparticles have been well characterized for their anticancer efficacy; however, little detail on RNA nanoparticle pathology and safety is known. Here, we report the in vitro and in vivo assessment of the pathology and safety aspects of different RNA nanoparticles including RNA three-way junction (3WJ) harboring 2'-F modified pyrimidine, folic acid, and Survivin siRNA, as well as the RNA four-way junction (4WJ) harboring 2'-F modified pyrimidine and 24 copies of SN38. Both animal models and patient serum were investigated. In vitro studies include hemolysis, platelet aggregation, complement activation, plasma coagulation, and interferon induction. In vivo studies include hematoxylin and eosin (H&E) staining, hematological and biochemical analysis as the serum profiling, and animal organ weight study. No significant toxicity, side effect, or immune responses were detected during the extensive safety evaluations of RNA nanoparticles. These results further complement previous cancer inhibition studies and demonstrate RNA nanoparticles as an effective and safe drug delivery vehicle for future clinical translations.

RNA four-way junction (4WJ) for spontaneous cancer-targeting, effective tumor-regression, metastasis suppression, fast renal excretion and undetectable toxicity.

The field of RNA therapeutics has been emerging as the third milestone in pharmaceutical drug development. RNA nanoparticles have displayed motile and deformable properties to allow for high tumor accumulation with undetectable healthy organ accumulation. Therefore, RNA nanoparticles have the potential to serve as potent drug delivery vehicles with strong anti-cancer responses. Herein, we report the physicochemical basis for the rational design of a branched RNA four-way junction (4WJ) nanoparticle that results in advantageous high-thermostability and -drug payload for cancer therapy, including metastatic tumors in the lung. The 4WJ nanostructure displayed versatility through functionalization with an anti-cancer chemical drug, SN38, for the treatment of two different cancer models including colorectal cancer xenograft and orthotopic lung metastases of colon cancer. The resulting 4WJ RNA drug complex spontaneously targeted cancers effectively for cancer inhibition with and without ligands. The 4WJ displayed fast renal excretion, rapid body clearance, and little organ accumulation with undetectable toxicity and immunogenicity. The safety parameters were documented by organ histology, blood biochemistry, and pathological analysis. The highly efficient cancer inhibition, undetectable drug toxicity, and favorable Chemical, Manufacturing, and Control (CMC) production of RNA nanoparticles document a candidate with high potential for translation in cancer therapy.

Challenges of artificial intelligence in medicine and dermatology.

Artificial intelligence (AI) in medicine and dermatology brings additional challenges related to bias, transparency, ethics, security, and inequality. Bias in AI algorithms can arise from biased training data or decision-making processes, leading to disparities in health care outcomes. Addressing bias requires careful examination of the data used to train AI models and implementation of strategies to mitigate bias during algorithm development. Transparency is another critical challenge, as AI systems often operate as black boxes, making it difficult to understand how decisions are reached. Ensuring transparency in AI algorithms is vital to gaining trust from both patients and health care providers. Ethical considerations arise when using AI in health care, including issues such as informed consent, privacy, and the responsibility for the decisions made by AI systems. It is essential to establish clear guidelines and frameworks that govern the ethical use of AI, including maintaining patient autonomy and protecting sensitive health information. Security is a significant concern in AI systems, as they rely on vast amounts of sensitive patient data. Protecting these data from unauthorized access, breaches, or malicious attacks is paramount to maintaining patient privacy and trust in AI technologies. Lastly, the potential for inequality arises if AI technologies are not accessible to all populations, leading to a digital divide in health care. Efforts should be made to ensure that AI solutions are affordable, accessible, and tailored to the needs of diverse communities, mitigating the risk of exacerbating existing health care disparities. Addressing these challenges is crucial for AI's responsible and equitable integration in medicine and dermatology.

The role of glucagon-like peptide 1 receptor agonists for weight control in individuals with acquired hypothalamic obesity-A systematic review.

Hypothalamic obesity does not respond well to conventional interventions for obesity. GLP-1 receptor agonists have mechanisms independent of the hypothalamus which may be potentially beneficial for managing hypothalamic obesity. This systematic review summarizes the efficacy and safety of GLP-1 receptor agonists use in hypothalamic obesity. A PRISMA-compliant systematic review was performed. Data was extracted from included studies and analysed based on change in weight, body mass index, glycaemic control, satiety, and safety profile with GLP-1 receptor agonist use. Ten studies comprising 5 case reports, 4 case series and 1 randomized-controlled trial included 54 patients (24 males, 30 females) with mean age of 25.2 (range 13-71) years with hypothalamic obesity who had received GLP-1 receptor agonists (exenatide = 48, liraglutide = 5 and dulaglutide = 1) over a mean duration of treatment of 12 (range 3-51) months. Mean weight reduction of 7.4 (SD 7.92) kg was observed in patients in whom weight was reported, with 85.7% of patients experiencing weight loss. All patients on liraglutide had weight reduction post-therapy. The sole trial had reported a non-significant reduction in BMI post-exenatide. Glycaemic control had either improved/maintained in all patients in whom this was measured. The main side effects of GLP-1 receptor agonist in individuals with hypothalamic obesity were nausea and vomiting; there were no major safety concerns. Based on limited published experience, GLP-1RA may be effective and safe for weight control in hypothalamic obesity, with the added benefit of improved glycaemic control in those with concurrent diabetes mellitus.

Subcarrier modulation based phase-coded coherent lidar.

This paper presents a lean subcarrier modulation-based phase-coded coherent lidar system with a non-quadrature receiver and sampling ratio lower than the Nyquist sampling ratio. Specifically, by utilizing the drawbacks of low Doppler tolerance in encoding signals, phase information can be obtained after pulse compression, and the mirror frequency introduced by real sampling can be negligible. Validation experiments based on inverse synthetic aperture lidar are performed, with the corresponding imaging results having a resolution superior to 4 cm, demonstrating our system's efficiency in phase acquisition that is free from frequency aliasing.

Multi-scale consistent self-training network for semi-supervised orbital tumor segmentation.

PURPOSE: Segmentation of orbital tumors in CT images is of great significance for orbital tumor diagnosis, which is one of the most prevalent diseases of the eye. However, the large variety of tumor sizes and shapes makes the segmentation task very challenging, especially when the available annotation data is limited. METHODS: To this end, in this paper, we propose a multi-scale consistent self-training network (MSCINet) for semi-supervised orbital tumor segmentation. Specifically, we exploit the semantic-invariance features by enforcing the consistency between the predictions of different scales of the same image to make the model more robust to size variation. Moreover, we incorporate a new self-training strategy, which adopts iterative training with an uncertainty filtering mechanism to filter the pseudo-labels generated by the model, to eliminate the accumulation of pseudo-label error predictions and increase the generalization of the model. RESULTS: For evaluation, we have built two datasets, the orbital tumor binary segmentation dataset (Orbtum-B) and the orbital multi-organ segmentation dataset (Orbtum-M). Experimental results on these two datasets show that our proposed method can both achieve state-of-the-art performance. In our datasets, there are a total of 55 patients containing 602 2D images. CONCLUSION: In this paper, we develop a new semi-supervised segmentation method for orbital tumors, which is designed for the characteristics of orbital tumors and exhibits excellent performance compared to previous semi-supervised algorithms.