Preoperative OCT-Derived Nasal Perifoveal Retinal Nerve Fiber Layer Thickness Predictively Correlates Long-Term Visual Acuity Post Oil Removal Surgery.

Purpose: With the widespread application of silicone oil in vitreoretinal surgery, the purpose of this study was to determine the risk factors of long-term vision loss 12 months post oil removal in retina-detached eyes treated with vitrectomy and silicone oil tamponade. Methods: Of the 592 patients approached, eligible eyes completed the investigation up to 12 months post-oil-removal. Eligible eyes underwent pars-plana vitrectomy following oil tamponade. Oil removal was performed after 3 to 28 months in different individuals, under the condition that the retina has reattached as well as the hemorrhage and inflammation has dissolved. Postoperative best-corrected visual acuity (BCVA), age, sex, and interval between tamponade and removal were recorded, and retinal thickness was determined using optical coherence tomography (OCT). Results: Fifty eyes of 50 participants aged 31 to 83 years were enrolled. BCVA (LogMAR) 12 months post-oil-removal improved in 25 of 40 (62.5%) patients, varying from 0.05 (20/22) to 1.0 (20/200) (mean ± SD = 0.55 ± 0.32). Pre-oil-removal nasal perifoveal retinal nerve fiber layer thickness varied from 16 to 83 µm (38.40 ± 18.50), and was significantly linked with post-oil-removal BCVA (0.5%, 95% confidence interval 0.0%-1.0%; P = 0.046). Conclusions: This study demonstrates the risk factors and prognosis of visual function after long-term regeneration post vitrectomy, oil tamponade, and oil removal, thereby underscoring the need for a complete, dynamic examination of retinal structure via OCT measurement. Related studies should be conducted on a larger scale to facilitate the stratification of late-period vision damage in retina-detached eyes. Translational Relevance: This study developed OCT-based clinical markers for the postoperative visual prognosis of eyes affected by retinal detachment.

The complex link between the gut microbiome and obesity-associated metabolic disorders: Mechanisms and therapeutic opportunities.

Microbial interactions are widespread and important processes that support the link between disease and microbial ecology. The gut microbiota is a major source of microbial stimuli that can have detrimental or beneficial effects on human health. It is also an endocrine organ that maintains energy homeostasis and host immunity. Obesity is a highly and increasingly prevalent metabolic disease and the leading cause of preventable death worldwide. An imbalance in the gut microbiome is associated with several diseases including obesity-related metabolic disorders. This review summarizes the complex association between the gut microbiome and obesity-associated metabolic diseases and validates the role and mechanisms of ecological dysregulation in the gut in obesity-associated metabolic disorders. Therapies that could potentially alleviate obesity-associated metabolic diseases by modulating the gut microbiota are discussed.

Umbilical cord blood-derived exosomes attenuate dopaminergic neuron damage of Parkinson's disease mouse model.

BACKGROUND: Umbilical cord blood (UCB) is a rich source of multifunctional stem cells characterized by low immunogenicity. Recent research in the fields of aging and regenerative medicine has revealed the potential of human umbilical cord blood-derived exosomes (UCB-Exos) in promoting wound healing, anti-aging, and regeneration. However, their role in neurodegenerative diseases, specifically Parkinson's disease (PD), remains unexplored. This study investigates the potential therapeutic effects and underlying mechanisms of UCB-Exos on PD. METHODS: Large extracellular vesicles (LEv), Exos, and soluble fractions (SF) of human UCB plasma were extracted to investigate their effects on motor dysfunction of the MPTP-induced PD mouse model and identify the key components that improve PD symptoms. UCB-Exos were administered by the caudal vein to prevent or treat the PD mouse model. The motor function and pathological markers were detected. Differentially expressed gene and KEGG enrichment pathways were screened by transcriptome sequence. MN9D and SH-SY5Y cells were cultured and evaluated for cell viability, oxidative stress, cell cycle, and aging-related indexes by qRT-PCR, western blot, immunofluorescence, and flow cytometry. The protein expression level of the MAPK p38 and ERK1/2 signaling pathway was detected by western blot. RESULTS: We observed that LEv, Exos, and SF all exhibited potential in ameliorating motor dysfunction in MPTP-induced PD model mice, with UCB-Exos demonstrating the most significant effect. UCB-Exos showed comparable efficacy in preventing and treating motor dysfunction, cognitive decline, and substantia nigra pathological damage in PD mice. Further investigations revealed that UCB-Exos could potentially alleviate oxidative damage, aging and degeneration, and energy metabolism disorders in neurons. Transcriptome sequencing results corroborated that genes differentially expressed due to UCB-Exos were primarily enriched in the neuroactive ligand-receptor interaction, Dopaminergic synapse, and MAPK signaling pathway. We also observed that UCB-Exos significantly inhibited the hyperphosphorylation of the MAPK p38 and ERK1/2 signaling pathways both in vitro and in vivo. CONCLUSIONS: Our study provides a comprehensive evaluation of UCB-Exos on the neuroprotective effects and suggests that inhibition of hyperphosphorylation of MAPK p38 and ERK 1/2 signaling pathways by regulating transcription levels of HspB1 and Ppef2 may be the key mechanism for UCB-Exos to improve PD-related pathological features.

Precise tracking of nanoparticles in plant roots.

One of the foremost challenges in nanobiotechnology is obtaining direct evidence of nanoparticles' absorption and internalization in plants. Although confocal laser scanning microscopy (CLSM) or transmission electron microscopy (TEM) are currently the most commonly used tools to characterize nanoparticles in plants, subjectivity of researchers, incorrect sample handling, inevitable fluorescence leakage and limitations of imaging instruments lead to false positives and non-reproducibility of experimental results. This protocol provides an easy-to-operate dual-step method, combining CLSM for macroscopic tissue examination and TEM for cellular-level analysis, to effectively trace single particles in plant roots with accuracy and precision. In addition, we also provide detailed methods for processing plant materials before imaging, including cleaning, and staining, to maximize the accuracy and reliability of imaging. This protocol involves currently commonly used nanomaterial types, such as metal-based and doped carbon-based materials, and enables accurate localization of nanoparticles with different sizes at the cell level in Arabidopsis thaliana root samples either through contrast or element mapping analysis. It serves as a valuable reference and benchmark for scholars in plant science, chemistry and environmental studies to understand the interaction between plant roots and nanomaterials and to detect the distribution of nanomaterials in plants. Excluding plant culture time, the protocol can be completed in 4-5 d.

Contribution of ferroptosis and SLC7A11 to light-induced photoreceptor degeneration.

Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss. Ferroptosis has been demonstrated to be associated with retinal degenerative diseases. However, the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored. Bioinformatics and biochemical analyses in this study revealed xC-, solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model. This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway, through which cystine depletion, iron ion accumulation, and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment. We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo. Conversely, solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H2O2-induced ferroptosis of 661W cells. These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.

Sestrin2 knockout exacerbates high-fat diet induced metabolic disorders and complications in female mice.

BACKGROUND: Obesity and its associated complications raise significant public concern, revealing gender disparities in the susceptibility to metabolic disorders, with females often displaying greater resistance to obesity-related metabolic disorder than males. Sestrin2 is a crucial protein involved in metabolism and energy balance. This study seeks to explore whether Sesn2 knockout (KO) exacerbates high-fat diet (HFD) induced obesity in female mice. METHODS: Female mice with wild-type (WT) and Sesn2 KO were subjected to a 12-week regimen of normal diet or HFD. Using a Body Composition Analyzer, body composition was gauged. Biochemical assays encompassed glucose, lipid, and liver function measurements, alongside 24-hour urine albumin excretion. Echocardiographic evaluation assessed cardiac function. Histopathological analysis of key metabolic tissues (liver, kidney, and heart tissues) were conducted. Western blotting or qRT-PCR evaluated key proteins and genes linked to inflammation, mitochondrial, and lipid metabolism in adipose tissues. RESULTS: In comparison to mice fed a regular diet, those on a HFD exhibited significant increases in body weight and fat mass. Notably, Sesn2 KO further aggravated obesity, showcasing the most pronounced metabolic anomalies: elevated body weight, fat mass, impaired glucose tolerance, and insulin sensitivity, alongside heightened levels of free fatty acids and triglycerides. Additionally, KO-HFD mice displayed exacerbated multi-tissue impairments, including elevated hepatic enzymes, increased urinary albumin excretion, compromised cardiac function, and accumulation of lipids in the liver, kidney, and heart. Moreover, adipose tissue showcased altered lipid dynamics and function, characterized by enhanced triglyceride breakdown and modified adipokine levels. Browning was diminished, along with decreased Pgc1α and Sirt1 in KO-HFD mice. CONCLUSION: Sesn2 KO exacerbates HFD-induced obesity and metabolic disorders in female mice. These findings underscore Sestrin2's novel role as a regulator of obesity in female mice.

Comprehensive assessment of the impact of intravitreal faricimab on retinal diseases: A systematic review, meta-analysis, and trial sequential analysis.

BACKGROUND: Faricimab stands as the inaugural and sole bispecific antibody approved by the US Food and Drug Administration (FDA) for intravitreal injection. Nonetheless, the efficacy and safety of intravitreal faricimab remained uncertain. OBJECTIVES: The purpose of this study was to evaluate faricimab. METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (CRD42023398320). Five databases (Pubmed, Embase, Web of science, Cochrane Library, ClinicalTrials gov) were searched. We calculated pooled standard mean difference or odds ratio with 95 % confident interval under a random-effect model or fixed-effect model. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was employed to ascertain the reliability of the analyses. Trial sequential analysis was performed to gauge the statistical reliability of the data in the cumulative meta-analysis. RESULTS: 8 studies (3975 participants) were included. The use of faricimab was associated with central subfield thickness (CST) change, but no difference was found in other primary efficacy outcomes. Apart from that, a correlation was observed between the use of faricimab and the risk of vitreous floaters. Based on TSA, strong evidence indicates that compared to the control group, faricimab aided in reducing CST but increasing the risk of vitreous floaters. CONCLUSIONS: In this study, a correlation existed between the use of faricimab and a reduction in CST, indicating a superior therapeutic effect. Moreover, participants treated with faricimab demonstrated a higher risk of vitreous floaters. More randomized controlled trials are essential to further explore the efficacy and safety of faricimab.

Publication trends of Leber congenital amaurosis researches: a bibliometric study during 2002-2022.

AIM: To analyze the changes in scientific output relating to Leber congenital amaurosis (LCA) and forecast the study trends in this field. METHODS: All of the publications in the field of LCA from 2002 to 2022 were collected from Web of Science (WOS) database. We analyzed the quantity (number of publications), quality (citation and H-index) and development trends (relative research interest, RRI) of published LCA research over the last two decades. Moreover, VOSviewer software was applied to define the co-occurrence network of keywords in this field. RESULTS: A total of 2158 publications were ultimately examined. We found that the focus on LCA kept rising and peaked in 2015 and 2018, which is consistent with the development trend of gene therapy. The USA has contributed most to this field with 1162 publications, 56 674 citations and the highest H-index value (116). The keywords analysis was divided into five clusters to show the hotspots in the field of LCA, namely mechanism-related, genotype-related, local phenotype-related, system phenotype-related, and therapy-related. We also identified gene therapy and anti-retinal degeneration therapy as a major focus in recent years. CONCLUSION: Our study illustrates historical research process and future development trends in LCA field. This may help to guide the orientation for further clinical diagnosis, treatment and scientific research.

Robust Edge States of Quasi-1D Material Ta2NiSe7 and Applications in Saturable Absorbers.

The helical edge states (ESs) protected by underlying Z2 topology in two-dimensional topological insulators (TIs) arouse upsurges in saturable absorptions thanks to the strong photon-electron coupling in ESs. However, limited TIs demonstrate clear signatures of topological ESs at liquid nitrogen temperatures, hindering the applications of such exotic quantum states. Here, we demonstrate the existence of one-dimensional (1D) ESs at the step edge of the quasi-1D material Ta2NiSe7 at 78 K by scanning tunneling microscopy. Such ESs are rather robust against the irregularity of the edges, suggesting a possible topological origin. The exfoliated Ta2NiSe7 flakes were used as saturable absorbers (SAs) in an Er-doped fiber laser, hosting a mode-locked pulse with a modulation depth of up to 52.6% and a short pulse duration of 225 fs, far outstripping existing TI-based SAs. This work demonstrates the existence of robust 1D ESs and the superior SA performance of Ta2NiSe7.

Multimodal Eye Imaging, Retina Characteristics, and Psychological Assessment Dataset.

The eyes provide insights into psychology, potentially offering a distinctive perspective for psychological health profiles. However, there exist a notable deficiency in datasets that simultaneously encompass eye features and psychological assessments. To address this gap, our study presents a dataset that included Fundus Photography, Psychological Assessment, Retina Characteristics, and Multimodal Imaging (FPRM). FPRM dataset comprise fundus images at different wavelengths (548 nm and 605 nm), image of oxygen saturation for the retina and 8 specific retinal vessels, videos of retinal blood flow and pupillary light reflex, along with 61 items of multimodal quantitative measurement from 384 participants. Additionally, it features psychological assessments across five dimensions (geriatric depression, generalized anxiety disorder, insomnia, activities of daily living, and deterioration), accompanied by fundus photographs and 6 items of retina characteristics from 1683 participants. FPRM dataset is the first to integrate multimodal ophthalmic data and psychological assessments, not only advancing the development of machine learning applications but also facilitating in-depth research into the relationship between eye health and psychological health profiles.

Efficacy and safety of efdamrofusp alfa versus aflibercept in participants with neovascular age-related macular degeneration: a randomized, double-masked, active-controlled, non-inferiority, phase 2 trial.

PURPOSE: To evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN: Randomized, double-masked, multicenter, active-controlled, non-inferiority phase 2 study PARTICIPANTS: A total of 231 treatment-naïve and previously treated participants with active choroidal neovascularization secondary to nAMD were enrolled. METHODS: Eligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa or 2 mg aflibercept groups. Participants in all groups received three initial monthly loading doses, followed by treatment every 8 weeks with assessment every 4 weeks up to week 52. MAIN OUTCOME MEASURES: The primary endpoint was the mean BCVA change from baseline to week 36. The pre-specified noninferiority margin was set as -5 letters (80% CI). RESULTS: Each treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were +10.6, +11.4, +12.0 letters, respectively; Least Squares (LS) mean difference were -1.4 (80% CI: -3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and -0.6 (80% CI: -2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups. CONCLUSIONS: Efdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile.

Cost-Effectiveness of Varicella Vaccination for 1-4-Year-Olds in Shanghai, China.

INTRODUCTION: Varicella has not yet been included in the National Immunization Program (NIP) in China, and varicella vaccination strategies vary by region. To determine the optimal varicella vaccination strategy in Shanghai, China, the cost-effectiveness and 5-year costs of 5 immunization scenarios were analyzed. METHODS: A static decision tree-Markov model was developed in 2022 to assess the cost-effectiveness and 5-year costs of voluntary and routine varicella vaccination programs in the 2019 birth cohort in Shanghai from a societal perspective. Parameters were collected in 2022 from the varicella surveillance system, a questionnaire survey of 414 guardians of patients with childhood varicella, and semi-structured interviews with 20 experts on varicella outbreaks from different institutions in Shanghai. The outcomes included varicella cases avoided, quality-adjusted life year (QALY) loss, and incremental costs per QALY (ICER). The 5-year costs were compared with local medical expenditures. RESULTS: Among the 5 scenarios, one dose of routine varicella vaccination was the most cost-saving (USD 70.2) and cost-effective (Dominant) with a 5-year immunization expenditure of USD 9.9 million. Two doses of routine varicella vaccination had the highest QALY (29.9), and its ICER (USD 791.9/QALY) was below the willingness-to-pay threshold (USD 5,203-23,767/QALY). The 5-year immunization expenditure was USD 19.8 million. The effectiveness and price of vaccines, vaccination coverage, and per capita income are the 4 main factors that affect ICERs. CONCLUSIONS: In Shanghai, the 2 doses of routine varicella vaccination strategy for 1- and 4-year-olds with a 95% coverage rate was found to be the optimal varicella immunization strategy.

Associations of Socioeconomic Status Inequity with Incident Age-related Macular Degeneration in Middle-Aged and Elderly Population.

Background: The relationship between socioeconomic status (SES) inequity and incident age-related macular degeneration (AMD) remains unclear. We aim to investigate whether low SES increases the risk of AMD and to explore the effect of a healthy lifestyle on this association. Methods: This prospective cohort study included 316,663 UK Biobank individuals. SES inequity was identified via latent class analysis using education, household income, and occupational status. Healthy lifestyle score was calculated based on smoking, alcohol drinking, and physical activity (PA). Incident AMD was defined according to diagnosis records. Cox proportional hazards models were used to evaluate the relationship of low SES and AMD. Interrelationships of healthy lifestyle score on SES-AMD association were explored, including modification, mediation, and joint effects. Results: During the average 12.2 years of follow-up, 6,355 AMD cases were diagnosed. Participants with medium SES (hazard ratio: 1.10 [95% confidence interval (CI) 1.01 to 1.21]) and low SES (hazard ratio: 1.22 [95% CI 1.11 to 1.34]) had an increased risk of incident AMD compared to participants with high SES. PA significantly affected this association. Moreover, the association between low SES and AMD was significantly mediated (11.3%, 95% CI: 6.56 to 23.0) by smoking. Similarly, alcohol drinking suppressed (9.59%, 95% CI: 4.00 to 23.2) the association between high SES and AMD. Besides, a significant joint effect of SES and healthy lifestyle score was found. Conclusions: We provide further evidence for the relationship of socioeconomic inequity, healthy lifestyle, and incident AMD. Future public health strategies should aim to reduce socioeconomic inequity to prevent AMD.

Publication trends of vascular endothelial growth factor (VEGF) and anti-VEGF treatment in neovascular age-related macular degeneration during 2001-2020: a 20-year bibliometric study.

PURPOSE: This study sought to provide an overview of the current research and further analyze publication trends in the field of vascular endothelial growth factor (VEGF) and anti-VEGF treatment for neovascular age-related macular degeneration (NVAMD). METHODS: We downloaded all related publications from 2001 to 2020 from the Web of Science Core Collection and conducted a bibliometric analysis using the bibiometrix package in R programming software. RESULTS: A total of 3717 publications were included in the analysis. The USA contributed the largest number of publications (1443), and achieved the highest number of citations (74,946) and H-index value (28). Johns Hopkins University, USA, was the top institution with the most publications, and Peter A. Campochiaro was the most productive professor at The Wilmer Eye Institute, USA. 9.60% of the total publications were from the Journal of Retinal and Vitreous Diseases. Trend analysis demonstrated that anti-VEGF therapy was introduced in early 2000 after steroids, and the last 2 decades have witnessed the blossom of several anti-VEGF agents. "Treat-and-extend" and "resistance" were two popular trend topics in recent years. CONCLUSIONS: The USA occupies a dominant position in the research field of VEGF and anti-VEGF treatments in NVAMD. Steroid administration, photodynamic therapy, and anti-VEGF therapy have been pivotal advances in the treatment of NVAMD patients over the past 2 decades. Limited acting period and resistance are potential investigation directions in future studies.

Metagenomic and metabolomic analysis showing the adverse risk-benefit trade-off of the ketogenic diet.

BACKGROUND: Ketogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity. METHODS: Male mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents. RESULTS: Obese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity. CONCLUSIONS: The study suggest that the ketogenic diet had an unfavorable risk-benefit trade-off and may compromise metabolic homeostasis in obese mice.

Donor and recipient hematopoietic stem and progenitor cells mobilization in liver transplantation patients.

BACKGROUND: Hematopoietic stem and progenitor cells (HSPCs) mobilize from bone marrow to peripheral blood in response to stress. The impact of alloresponse-induced stress on HSPCs mobilization in human liver transplantation (LTx) recipients remains under-investigated. METHODS: Peripheral blood mononuclear cell (PBMC) samples were longitudinally collected from pre- to post-LTx for one year from 36 recipients with acute rejection (AR), 74 recipients without rejection (NR), and 5 recipients with graft-versus-host disease (GVHD). 28 PBMC samples from age-matched healthy donors were collected as healthy control (HC). Multi-color flow cytometry (MCFC) was used to immunophenotype HSPCs and their subpopulations. Donor recipient-distinguishable major histocompatibility complex (MHC) antibodies determined cell origin. RESULTS: Before LTx, patients who developed AR after transplant contained more HSPCs in PBMC samples than HC, while the NR group patients contained fewer HSPCs than HC. After LTx, the HSPC ratio in the AR group sharply decreased and became less than HC within six months, and dropped to a comparable NR level afterward. During the one-year follow-up period, myeloid progenitors (MPs) biased differentiation was observed in all LTx recipients who were under tacrolimus-based immunosuppressive treatment. During both AR and GVHD episodes, the recipient-derived and donor-derived HSPCs mobilized into the recipient's blood-circulation and migrated to the target tissue, respectively. The HSPCs percentage in blood reduced after the disease was cured. CONCLUSIONS: A preoperative high HSPC ratio in blood characterizes recipients who developed AR after LTx. Recipients exhibited a decline in blood-circulating HSPCs after transplant, the cells mobilized into the blood and migrated to target tissue during alloresponse.

Integrated image-based deep learning and language models for primary diabetes care.

Primary diabetes care and diabetic retinopathy (DR) screening persist as major public health challenges due to a shortage of trained primary care physicians (PCPs), particularly in low-resource settings. Here, to bridge the gaps, we developed an integrated image-language system (DeepDR-LLM), combining a large language model (LLM module) and image-based deep learning (DeepDR-Transformer), to provide individualized diabetes management recommendations to PCPs. In a retrospective evaluation, the LLM module demonstrated comparable performance to PCPs and endocrinology residents when tested in English and outperformed PCPs and had comparable performance to endocrinology residents in Chinese. For identifying referable DR, the average PCP's accuracy was 81.0% unassisted and 92.3% assisted by DeepDR-Transformer. Furthermore, we performed a single-center real-world prospective study, deploying DeepDR-LLM. We compared diabetes management adherence of patients under the unassisted PCP arm (n = 397) with those under the PCP+DeepDR-LLM arm (n = 372). Patients with newly diagnosed diabetes in the PCP+DeepDR-LLM arm showed better self-management behaviors throughout follow-up (P < 0.05). For patients with referral DR, those in the PCP+DeepDR-LLM arm were more likely to adhere to DR referrals (P < 0.01). Additionally, DeepDR-LLM deployment improved the quality and empathy level of management recommendations. Given its multifaceted performance, DeepDR-LLM holds promise as a digital solution for enhancing primary diabetes care and DR screening.

Parental willingness to pay and preference for human papillomavirus vaccine for girls aged 9-14 in subsidy scenarios in Shanghai, China.

Multiple studies have documented low human papillomavirus (HPV) vaccine uptake among Chinese girls. It remains crucial to determine the parental willingness to pay (WTP) HPV vaccine for girls. We conducted a cross-sectional study recruiting 3904 parents with girls aged 9-14 in Shanghai, China, employing an online questionnaire with a convenience sampling strategy. Parental WTP, both range of payment and estimated point value, were determined for themselves (or wives) and daughters. HPV vaccine uptake was 22.44% in mothers and 3.21% in daughters. Respondents favored WTP ≤ 1000 CNY/138 USD for themselves (or wives), whereas showed increasing WTP along with valency of HPV vaccine for daughters (2-valent: 68.62% ≤1000 CNY/138 USD; 4-valent: 56.27% 1001-2000 CNY/138-277 USD; 9-valent: 65.37% ≥2001 CNY/277 USD). Overall, respondents showed higher WTP for daughters (median 2000 CNY/277 USD; IQR 1000-3600 CNY/138-498 USD) than for themselves (2000 CNY/277 USD; 1000-3500 CNY/138-483 USD) or wives (2000 CNY/277 USD; 800-3000 CNY/110-414 USD) (each p < .05). Furthermore, parental WTP was higher for international vaccine and 9-valent vaccine (each p < 0.05). Between two assumed government subsidy scenarios, parental preference for 9-valent vaccine remained consistently high for daughters (approximately 24% in each scenario), whereas preference for themselves (or wives) was sensitive to payment change between the subsidy scenarios. Using a discrete choice experiment, we found domestic vaccine was commonly preferred; however, certain sociodemographic groups preferred multivalent HPV vaccines. In conclusion, the valency of HPV vaccine may influence parental decision-making for daughters, in addition to vaccine price. Our findings would facilitate tailoring the HPV immunization program in China.

Exploring potential predictive biomarkers through historical perspectives on the evolution of systemic therapies into the emergence of neoadjuvant therapy for the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), a type of liver cancer, ranks as the sixth most prevalent cancer globally and represents the third leading cause of cancer-related deaths. Approximately half of HCC patients miss the opportunity for curative treatment and are then limited to undergoing systemic therapies. Currently, systemic therapy has entered the era of immunotherapy, particularly with the advent of immune-checkpoint inhibitors (ICIs), which have significantly enhanced outcomes for patients with advanced HCC. Neoadjuvant treatment for HCC has become a possibility-findings from the IMbrave 050 trial indicated that ICIs offer the benefit of recurrence-free survival for high-risk HCC patients post-resection or local ablation. However, only a small fraction of individuals benefit from systemic therapy. Consequently, there is an urgent need to identify predictive biomarkers for treatment response and outcome assessment. This study reviewed the historical progression of systemic therapy for HCC, highlighting notable therapeutic advancements. This study examined the development of systemic therapies involving conventional drugs and clinical trials utilized in HCC treatment, as well as potential predictive biomarkers for advanced and/or locally advanced HCC. Various studies have revealed potential biomarkers in the context of HCC treatment. These include the association of dendritic cells (DCs) with a favorable response to neoadjuvant therapy, the presence of enriched T effector cells and tertiary lymphoid structures, the identification of CD138+ plasma cells, and distinct spatial arrangements of B cells in close proximity to T cells among responders with locally advanced HCC receiving neoadjuvant cabozantinib and nivolumab treatment. Furthermore, pathological response has been associated with intratumoral cellular triads consisting of progenitor CD8+ T cells and CXCL13+ CD4+ T helper cells surrounding mature DCs in patients receiving neoadjuvant cemiplimab for resectable HCC. Despite no widely recognized predictive biomarkers for HCC individualized treatment, we believe neoadjuvant trials hold the most promise in identifying and validating them. This is because they can collect multiple samples from resectable HCC patients across stages, especially with multi-omics, bridging preclinical and clinical gaps.