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Abstract This study investigated alterations in the foveal microvasculature following the administration of 0.125% atropine in myopic children. In this prospective study, 63 eyes from 36 individuals aged 5–18 years with myopia were administered 0.125% atropine for myopia control. After administration, foveal microvascular parameters such as the area and perimeter of the foveal avascular zone (FAZ), the acircularity index (AI) of FAZ, and foveal vessel density were evaluated longitudinally. The effect of atropine on foveal microvasculature was analyzed using a linear mixed model. One month after atropine application, the area and perimeter of FAZ significantly decreased (p = 0.014 and 0.041). A significant decrease in vessel density within the 300-µm wide annulus around FAZ and an increase in the AI of the FAZ were observed in the initial 3-month period (p = 0.035 and p = 0.047, respectively). However, changes in the FAZ area, perimeter, AI and foveal vessel density throughout the follow-up were not significant. These findings suggest that 0.125% atropine may induce transient changes in FAZ size and foveal vessel density, but its overall safety in managing myopia is supported by the stability of foveal parameters over time.

Abstract Extracorporeal cardiopulmonary resuscitation (ECPR) improves survival for prolonged cardiac arrest (CA) but carries significant risks and costs due to ECMO. Previous predictive models have been complex, incorporating both clinical data and parameters obtained after CPR or ECMO initiation. This study aims to compare a simpler clinical-only model with a model that includes both clinical and pre-ECMO laboratory parameters, to refine patient selection and improve ECPR outcomes. Medical records between January 2012 and January 2019 in our institution were retrospectively reviewed. Patients who met the following criteria were enrolled in the ECPR program: age 18–75 years, CCPR started with CA in

Abstract One of the major problem in the cultivation of sugar beets is continuous cropping obstacle in China. In order to evaluate the effects of continuous cropping year on the photosynthetic performance, dry matter accumulation, and distribution of sugar beet, this study was conducted in the 2020–2021 crop season at the Agriculture and Forestry Sciences of Ulanqab, Inner Mongolia. A split plot system arrangement with three replications was set up to carry out the field testing. The main plots had five planting years, with the a first cropping of each growing season serving as the control (CK) and four continuous cropping treatments for one, two, three, and four years (designated as C1, C2, C3, and C4, respectively). The subplot consisted of two fertilization treatments designated as 0 kg ha−1 bio-organic fertilization (N) and 6000 kg ha−1 bio-organic fertilization (Y). The findings demonstrated that the continuous cropping impeded sugar beet photosynthesis as well as the accumulation and dispersion of the dry matter in leaf, petiole, and root. The intercellular CO2 concentration (Ci), transpiration rate (Tr), stomatal conductance (Gs), net photosynthetic rate (Pn), and SPAD value were dramatically dropped as the number of continuous cropping years increased under the crop. Compared with CK, the SPAD value, Pn, Ci, Tr, Gs of continuous cropping treatments were significantly reduced by an average of 10.09–48.21%, 14.60–43.19%, 12.00–42.86%, 7.77–43.83%, 9.61–37.68%, respectively. The dry matter accumulation of leaf, petiole, root, and the whole plant were also reduced by 11.86–49.61%, 9.58–44.77%, 17.26–53.76%, and 10.62–49.79%, respectively. With the increasing of continuous cropping year, the growth of sugar beet was significantly inhibited. Study revealed that continuous cropping had an impact on the distribution of dry matter accumulation of sugar beet; it considerably raised the dry matter ratio above ground, lowered the dry matter ratio below ground, and prevented dry matter from moving from aboveground towards root, whitch caused a decline in sugar beet root production and disturbed the root shoot ratio. Compared with CK, the root shoot ratio significantly decreased by 3.62–19.76%. Under continuous cropping stystem, the application of bio-organic fertilizer had an effect on promoting the photosynthesis of sugar beet, and regulating the distribution and transport of dry matter. The effects of bio-organic fertilizer were significantly under continuous cropping for 1–2 years. Compared with C1N and C2N, the Pn, Ci, Tr, Gs of C1Y and C2Y were significantly increased by 12.79–22.50%, 14.76–16.47%, 4.76–13.08%, 8.51–12.70%, and 13.69–18.91%, 12.17–14.60%, 5.71–15.14%, 7.58–15.41%, respectively. Dry matter accumulation of leaf, petiole, root, whole plant were significantly increased by 8.32–16.18%, 10.80–13.33%, 14.93–20.13%, 14.12–15.43%, and 10.65–15.32%, 6.58–15.63%, 15.37–20.94%, 12.68–16.85%, respectively. Nonetheless, the root shoot ratio increased by 4.58–8.56% and 4.52–7.35%. Above all, Under continuous cropping conditions, the application of 6000 kg ha−1 bio-organic fertilizer could effectively promote the photosynthesis of sugar beet, and better regulate the distribution and transport of dry matter of sugar beet. These results can provide scientific basis for bio-organic fertilizer to alleviate the problem of sugar beet continuous cropping.

Abstract This study evaluated the effectiveness of intraovarian platelet-rich plasma (PRP) injection in improving ovarian response and embryo quality in IVF patients with poor embryo quality in previous controlled ovarian hyperstimulation (COH) cycles. 74 patients participated, with 30 in the control group and 44 in the PRP group. PRP was injected during the follicular phase for the PRP group. The control group completed two COH cycles, while the PRP group underwent COH cycles before and after the PRP injection. In the first COH cycle, there were no significant differences between groups. However, in the second COH cycle, the PRP group showed significant improvements: the number of fertilized oocytes increased (5.2 ± 3.6 vs. 3.3 ± 3.5, p = 0.011), total blastocysts (1.7 ± 1.5 vs. 0.5 ± 0.7, p

Abstract Protein phosphatase PPM1B, a member of the serine/threonine phosphatase family, has been implicated in various human cancers. In this study, our objective was to investigate the role of PPM1B in GC growth and explore the underlying mechanisms. Our findings revealed that PPM1B expression was downregulated in GC tissues, and higher levels of PPM1B expression were associated with improved overall survival in GC patients. Overexpression of PPM1B significantly inhibited cell proliferation, induced G1 phase cell cycle arrest, and suppressed tumor growth. Conversely, knockdown or knockout of PPM1B yielded opposite effects. Mechanistically, we identified that PPM1B exerted its inhibitory role in GC cell growth and cell cycle regulation through the TRIM25/PPM1B/CDK2 signaling pathway. Specifically, we demonstrated that TRIM25 physically interacts with PPM1B, leading to enhanced degradation of PPM1B and subsequent modulation of CDK2 phosphorylation and GC cell growth. PPM1B emerges as a potential prognostic biomarker and therapeutic target in GC. These findings hold clinical significance by offering opportunities to improve diagnosis and treatment strategies for GC patients. Furthermore, this study provides novel insights into the pathogenesis and progression of GC, expanding our understanding of this disease.

Abstract The terrestrial environment is a significant source of anthropogenic debris emissions. While most studies on anthropogenic debris focus on the marine environment, our research delves into the effects of human activity on anthropogenic debris ingestion by studying the carcasses of feral pigeons. From January to June 2022, we collected the gastrointestinal tracts (GI tracts) of 46 pigeon carcasses in Taipei, Taiwan’s capital city. The results revealed that 224 anthropogenic debris samples were found, with the dominant form being fibers (71.9%), which are primarily black (29.9%). Fourier transform infrared spectroscopy (FTIR) revealed that the main component of anthropogenic debris is polyethylene (PE) (20.5%), followed by anthropogenic cellulose (19.2%) and various other plastics. This study revealed that the amount of anthropogenic debris and chemical composition in the GI tract significantly increase with increasing human activity. These results prove that feral pigeons are valuable indicators for monitoring anthropogenic debris pollution in urban ecosystems. On the other hand, past research focused on analyzing microplastics, but we confirmed that the GI tract of pigeons has a high proportion of anthropogenic cellulose. Importantly, future studies should consider the potential impacts of anthropogenic cellulose in terrestrial ecosystems, as this could have significant implications for ecosystem health.

Abstract This study explored aural perception in children with autism using an aural perception test and electrophysiological responses to sound stimuli. The results demonstrated unique responses to sound stimuli at different sound intensity levels, emphasising the need for customised noise-control strategies targeting specific troublesome frequencies. To address this issue, headset intervention technology with a hybrid active noise control system integrated with an aural perception controlling function was developed for children with autism with distinct auditory perception based on their psychoacoustic characteristics. The results showed that the noise-control strategy was effective in mitigating unpleasant feelings and reducing the loudness and sharpness of daily stimuli. The proposed aural perception controllable headset can minimise noise, leading to a noticeable reduction in the magnitude of the auditory evoked potential at the midline central brain region for children with autism exposed to certain sounds, such as heavy vehicles and thunder, providing a more pleasant aural perception. A diminished auditory evoked potential response was associated with lower annoyance and pleasant aural perception. This study suggests that the proposed aural-perception-based noise-control method has the potential to alleviate behaviours related to auditory hyperreactivity in children with autism.

Abstract According to the importance of railway safety, it is crucial to build a smart railway traffic safety system in Taiwan, especially there are often to see related accidents. Therefore, this study aimed to build a smart railway traffic safety system using the integration of object detection, segmentation, machine learning, and notification system. First, the Mask R-CNN model was applied to automatically build the digital boundaries of railway, which achieved an average Interest of Union (IOU) of over 0.9. Then, the YOLO v3 model was applied to detect intrusions of railway, especially humans’ intrusion. The above object detection model achieved an Overall accuracy (OA) of over 90% for different classes, and an OA of 95.68% for human detection. The YOLO v3 model was also able to detect intrusion within different scenarios, such as nighttime, rainy daytime, and rainy nighttime. Moreover, the XGBoost model was applied to predict the sizes of intruding objects, which has a low MAE of 0.54 cm and an R2 score of 0.997. Finally, the LINE bot was applied to notify the related operators, including the above information, such as time of intrusion, locations, classes of intruding objects, sizes and the image of intrusion. The above implementation can be helpful for railway traffic safety monitoring, which may help related accidents prevention.

Abstract The aim of our study is to investigate whether adjunct neuromuscular electrical stimulation (NMES) therapy improves functional performance outcomes in children with cerebral palsy (CP) who have received botulinum toxin (BTX) injections. We searched the PubMed, Cochrane Library, CINAHL, EMBASE, and Scopus databases for randomized controlled trials studying the effects of NMES after BTX injection in children with CP from database inception to July 3, 2024. Two independent reviewers extracted data, and risks of bias were assessed using the PEDro scale for randomized controlled trials. We included 5 randomized controlled trials in this meta-analysis. NMES treatment following BTX injection resulted in greater functional performance outcomes compared with BTX injections alone (standardized mean difference = 0.57; 95% CI = 0.22 to 0.92). However, NMES following BTX injections did not significantly improve spasticity outcomes (standardized mean difference = 0.28; 95% CI = − 0.21 to 0.76). Despite including only a small number of trials, the present analysis demonstrated that NMES is an effective adjunct to BTX injections for managing CP in children. Further research must be conducted to refine these therapies, ensure better outcomes, and alleviate the burdens faced by individuals with CP.

Abstract Monoclonal antibodies (mAbs) constitute a new form of immunotherapy that has shown great success in long-term tumour control. These injectable drugs are managed and compounded by the Pharmacy Intravenous Admixture Services (PIVAS) staff in a specified sterile environment. This study utilized failure mode and effect analysis (FMEA) as a risk management tool to manage mAb drugs within the PIVAS. The nine-member multidisciplinary team mapped the processes; evaluated the severity, occurrence, and detection of each subprocess; and calculated the risk priority number (RPN). Further corrective actions were taken for high-risk steps, followed by re-evaluation and scoring to achieve a low-risk process. We identified seven major processes and twenty-eight subprocesses involved in the management of mAb drugs in PIVAS. A total of thirteen high-risk failure modes with an assigned RPN 1 were selected. This selection represents the first calculated RPN values, resulting in a total score of 3375. After a first round of evaluation and implementation of corrective actions, the RPN 2 score decreased to 464. Following a second round of the FMEA process, the RPN 3 score was further reduced to 51. Through refinement, we successfully mitigated the occurrence of high-risk failure modes of mAb drugs in PIVAS. These efforts are aimed at enhancing the safety and efficacy of mAb drugs, ultimately ensuring patient safety.

Abstract Understanding the underlying mechanisms regulating hair regeneration is crucial, especially given the increasing demand for effective drugs to treat hair loss, which remain not fully elucidated. In the present study, we found that lipid metabolism was attenuated in the scalp tissues of patients with androgenetic alopecia. Lipid supplementation in the culture medium upregulated hair growth-related genes and promoted the proliferation of human dermal papilla cells (DPCs). By using RNA-sequencing analysis and HIF-1α knockdown in DPCs, we found that HIF-1α is a potential candidate that governs lipid-reinforced upregulation of trichogenic genes. Finally, we assessed the hair growth-promoting effects of lipids using in vitro hair follicle organoids and found that lipids accelerated the elongation of hair-shaft-like structures. Our results highlight the importance of lipids in promoting hair growth through HIF-1 signaling, suggesting that this may be a promising target for the treatment of hair loss.

Abstract HIV acquisition has been found to be associated with increased risk of cardiometabolic syndrome in the past. In this study, we attempt to delineate the associated factors of metabolic syndrome among persons living with HIV in a single medical center in Taiwan using mostly integrase inhibitors-based regimen as HAART. A cross-sectional study involving all people living with HIV (PLWH) aged ≥ 18 years who visited MacKay Memorial Hospital, Taipei, Taiwan between September 7, 2022 to January 31, 2023 was performed. A modified National Cholesterol Education Program ATP III definition of metabolic syndrome was used to define metabolic syndrome and body mass index was used as surrogate for waist circumference. 809 PLWH participated in the study, in which 81.3% of patients were on integrase inhibitor-based HAART regimen. The prevalence of metabolic syndrome was 10.0%, which is markedly lower than those reported in the literature. Age was a significant risk factor for metabolic syndrome. HIV-related factors (CD4, viral load, HAART regimen) did not affect the presence of metabolic syndrome. Prevalence rate of metabolic syndrome appeared to have declined among PLWH compared to previous reports, possibly secondary to widespread use of integrase inhibitors. Age remains a strong risk factor for the development of metabolic syndrome among PLWH.

Abstract The COVID-19 pandemic has burdened healthcare systems globally. To curb high hospital admission rates, only patients with genuine medical needs are admitted. However, machine learning (ML) models to predict COVID-19 hospitalization in Asian children are lacking. This study aimed to develop and validate ML models to predict pediatric COVID-19 hospitalization. We collected secondary data with 2200 patients and 65 variables from Malaysian aged 0 to 12 with COVID-19 between 1st February 2020 and 31st March 2022. The sample was partitioned into training, internal, and external validation groups. Recursive Feature Elimination (RFE) was employed for feature selection, and we trained seven supervised classifiers. Grid Search was used to optimize the hyperparameters of each algorithm. The study analyzed 1988 children and 30 study variables after data were processed. The RFE algorithm selected 12 highly predicted variables for COVID-19 hospitalization, including age, male sex, fever, cough, rhinorrhea, shortness of breath, vomiting, diarrhea, seizures, body temperature, chest indrawing, and abnormal breath sounds. With external validation, Adaptive Boosting was the highest-performing classifier (AUROC = 0.95) to predict COVID-19 hospital admission in children. We validated AdaBoost as the best to predict COVID-19 hospitalization among children. This model may assist front-line clinicians in making medical disposition decisions.

Abstract Optimal management of T1 colorectal cancer (CRC) remains controversial. This study compared the long-term outcomes of endoscopic resection with additional surgical resection (ER + ASR) versus primary surgical resection (PS) in patients with T1 CRC and identified risk factors for lymph node metastasis (LNM). This retrospective cohort study included 373 patients with T1 CRC who underwent ER + ASR or PS between January 2010 and December 2020 at a tertiary center in Taiwan. Surgical and oncological outcomes, including recurrence rates, LNM, 5-year overall survival (OS), and 5-year recurrence-free survival (RFS) were compared. Univariate and multivariate analyses identified risk factors for LNM. No significant differences were observed between the ER + ASR and PS groups in surgical outcomes, recurrence rates, LNM, 5-year OS (93% vs. 89%, P = 0.18), or 5-year RFS (89% vs. 88%, P = 0.47). Patients with ≥ 2 high-risk factors had significantly lower 5-year OS and RFS compared to those with ≤ 1 risk factor (p

Abstract Despite advances in gastric cancer diagnosis and treatment, its prognosis remains poor owing to aggressive tumor progression and metastasis. As understanding the relevant molecular mechanisms is essential to effectively improve patient outcomes, we elucidated the role of Kindlin-1 in gastric cancer progression and metastasis. Kindlin-1 expression was analyzed in 359 gastric cancer tissue samples provided by Kangnam Sacred Heart Hospital and publicly available GSE datasets. Kindlin-1 showed significantly higher expression in gastric cancer tissues than that in normal tissues, and high Kindlin-1 expression was associated with poor prognosis. Further, the mRNA and protein expression of Kindlin-1 were high in gastric cancer cell lines, where they were associated with increased proliferation, migration, and invasion. Our findings demonstrated that Kindlin-1 regulated epithelial–mesenchymal transition-related genes through interaction with activated Wnt/β-catenin signaling. Notably, Kindlin-1 enhanced β-catenin expression and promoted its nuclear translocation from the cytoplasm, increasing TCF4 transcriptional activity and inducing gastric cancer progression and metastasis. Overall, these findings demonstrate that Kindlin-1 is upregulated in gastric cancer and activates Wnt/β-catenin signaling to promote cell proliferation and motility.

Abstract The accumulation and discharge amount of coal gangue are substantial, occupying significant land resources over time. Utilizing coal gangue as subgrade filler can generate notable economic and social benefits. Coal gangue coarse-grained soil (CGSF) was used to conduct a series of large-scale vibration compaction tests and large-scale triaxial tests. The results indicate that the maximum dry density of CGSF initially increases and then decreases with the increase in fractal dimension. The stress–strain curves of the samples exhibit a distinct nonlinear growth pattern. Analysis of the compaction effect suggests that the compaction degree of CGSF should not be lower than 93%. As the confining pressure increases, the extent of failure strength improvement due to increased compaction decreases. Additionally, the failure strength of samples initially increases and then decreases with the increase in coarse particle content. A modified quadratic polynomial fractal model gradation equation was proposed to describe the gradation of samples after particle breakage. Based on this, a new quantitative index for particle breakage was established. Analysis of particle breakage in samples revealed that higher confining pressure and greater coarse particle content lead to increased particle breakage. The breakage exhibited a significant size effect, and the impact of particle gradation on sample breakage was greater than that of confining pressure. The stress–strain relationship of CGSF was analyzed by using a logarithmic constitutive model, and the correlation between model parameters and the newly derived particle breakage index was generated. A constitutive model incorporating particle breakage for CGSF was established, and its accuracy was validated.

Abstract Trust and rapport are essential abilities for human–robot interaction. Producing emotional expressions in the robots’ faces is an effective way for that purpose. Androids can show human-like facial expressions of basic emotions. However, whether androids can show the facial expression of complex emotions remains unknown. In this experiment, we investigated the android Nikola’s ability to produce 22 dynamic facial expressions of complex emotions. For each video, 240 international participants (120 Japanese, 120 German) rated the emotions expressed by Nikola. For 13 complex emotions (i.e., amusement, appal, awe, boredom, contentment, coyness, hatred, hesitation, moral disgust, not face, pain, sleepiness, suspicion), participants of both samples rated the target emotion above the mean of other non-target emotions. Four emotions (bitterness, confusion, pride, relief) were rated above mean by one sample. For twelve of these emotions, target emotions were among the highest ranked. The results suggest that androids can produce the facial expressions of a wide range of complex emotions, which can facilitate human–robot interactions.

Abstract To enhance the mechanical properties and electrical conductivity of Al-Cu-Mg-based composites, aluminum matrix composites containing scandium (Sc) and graphene nanoplatelets (GNPs) were fabricated by means of stepwise ball milling, vacuum hot pressing sintering, and hot rolling techniques. When Sc and GNPs were incorporated at concentrations of 0.1 wt% and 0.2 wt% respectively, the resultant composites demonstrated a maximum tensile strength of 326.81 MPa, an elongation of 3.2%, an electrical conductivity of 46.95% IACS, and a hardness of 112.96 HV. In comparison with the 2024 aluminum alloy matrix, enhancements of 39%, 255%, 51% and 51.21% were witnessed in tensile strength, elongation, electrical conductivity, and hardness respectively. These improvements can be primarily ascribed to the addition of Sc, which facilitated the precipitation of solute atoms and enhanced the interfacial bonding between the GNPs and the matrix, as well as the remarkable heterogeneous layered microstructure induced by the incorporation of GNPs. This study presents a feasible approach to concurrently enhance the strength and electrical conductivity of composites through the combined addition of Sc and GNPs.

Abstract In the vascular system, angiotensin II (Ang II) mediated vasoconstriction by inducing the production of 20-hydroxyeicosatetraenoic acid (20-HETE). However, the role of 20-HETE in Ang II-induced cardiac dysfunction had yet to be fully elucidated. This study investigated the effects of Ang II on CYP4A expression and 20-HETE production in H9c2 cells using RT-qPCR, Western blot, and ELISA. The role of 20-HETE in Ang II-induced cardiac hypertrophy was examined using DHE, MitoSOX, and JC-1 staining to evaluate reactive oxygen species (ROS) generation and mitochondrial membrane potential changes. The ERK/Akt and CaN/NFAT3 signaling pathways were analyzed through Western blot. Ang II was found to promote CYP4A expression and 20-HETE production in H9c2 cells via an AT1 receptor-dependent mechanism. Additionally, the upregulation of AT1 receptor expression by 20-HETE further confirms its facilitatory effect on the Ang II signaling pathway. Inhibition of 20-HETE synthesis or blockade of its receptor, G-protein-coupled receptor 75 (GPR75), significantly reversed Ang II-induced cardiac hypertrophy. This reversal was closely associated with 20-HETE-induced ROS production, oxidative stress, and activation of the Ca2+/CaN/NFAT3 signaling pathway. This study demonstrated that 20-HETE mediated Ang II-induced cardiac hypertrophy and, for the first time, highlighted the significant role of the GPR75 receptor in this process. These findings suggested that targeting 20-HETE reduction or blocking its receptor action could offer a novel therapeutic approach for cardiovascular diseases associated with Ang II.

Abstract This article details the development of a next-word prediction model utilizing federated learning and introduces a mechanism for detecting backdoor attacks. Federated learning enables multiple devices to collaboratively train a shared model while retaining data locally. However, this decentralized approach is susceptible to manipulation by malicious actors who control a subset of participating devices, thereby biasing the model’s outputs on specific topics, such as a presidential election. The proposed detection mechanism aims to identify and exclude devices with anomalous datasets from the training process, thereby mitigating the influence of such attacks. By using the example of a presidential election, the study demonstrates a positive correlation between the proportion of compromised devices and the degree of bias in the model’s outputs. The findings indicate that the detection mechanism effectively reduces the impact of backdoor attacks, particularly when the number of compromised devices is relatively low. This research contributes to enhancing the robustness of federated learning systems against malicious manipulation, ensuring more reliable and unbiased model performance.

Abstract The role of pre-treatment HBV DNA levels on the prognosis of hepatitis B virus-related decompensated cirrhosis is unclear. This study investigated the effects of pre-treatment HBV DNA and other determinants on short-term and long-term survival of chronic hepatitis B (CHB) patients with decompensated cirrhosis. A total of 278 cirrhotic decompensated CHB patients treated with entecavir or tenofovir disoproxil fumarate were retrospectively enrolled. Cox regression models were used to analyze factors associated with all-cause mortality. The median follow-up time was 17 months (IQR2.17–58.94), during which 132 patients (47.4%) either died or underwent liver transplantation. The cumulative incidence of all-cause mortality was 16%, 29%, 34%, 39%, and 51% at the 1-month, 3-month, 6-month, 1-year, and 5-year follow-ups, respectively. Risk factors associated with 3-month all-cause mortality were age, presence of ascites and hepatic encephalopathy, baseline hepatitis flares, pre-treatment HBV DNA levels, and MELD scores. In the subgroup analysis, for 3-month all-cause mortality, significant associations of age, baseline hepatitis flares, and MELD scores with pre-treatment HBV DNA levels were observed (p for interaction were 0.005, 0.032, and 0.030, respectively). Risk factors associated with 5-year all-cause mortality were age, the presence of ascites and hepatic encephalopathy, and MELD scores. Liver functional reserve and age played a critical role in the prognosis of CHB patients with decompensated cirrhosis. Pre-treatment HBV DNA levels had an impact on short-term all-cause mortality, but not on long-term all-cause mortality.

Abstract To test for rates of inpatient palliative care (IPC) in metastatic testicular cancer patients receiving critical care therapy (CCT). Within the Nationwide Inpatient Sample (NIS) database (2008–2019), we tabulated IPC rates in metastatic testicular cancer patients receiving CCT, namely invasive mechanical ventilation (IMV), percutaneous endoscopic gastrostomy tube (PEG), dialysis for acute kidney failure (AKF), total parenteral nutrition (TPN) or tracheostomy. Univariable and multivariable logistic regression models addressing IPC were fitted. Of 420 metastatic testicular cancer patients undergoing CCT, 70 (17%) received IPC. Between 2008 and 2019, the rates of IPC among metastatic testicular cancer patients undergoing CCT increased from 5 to 19%, with the highest rate of 30% in 2018 (EAPC: + 9.5%; 95% CI + 4.7 to + 15.2%; p = 0.005). IPC patients were older (35 vs. 31 years, p = 0.01), more frequently had do not resuscitate (DNR) status (34 vs. 4%, p

Abstract Late-onset hypogonadism (LOH) refers to sexual and non-sexual symptoms in men caused by age-related decreases in circulating testosterone. Leydig cells (LCs) transplantation is considered to be one of a viable approach for LOH therapy, but the limited source of LCs limits the application of this approach. The aim of this study was to induce the directed differentiation of rat bone marrow mesenchymal stem cells (BMSCs) into LCs in vitro, and explore the potential involvement of Wnt/β-catenin signaling pathway in the differentiation process. BMSCs were extracted from rats and characterized by flow cytometry for positive rates of mesenchymal stem cell markers CD29, CD44, CD90, and the hematopoietic marker CD45. BMSCs were divided into three groups: Control, Wnt agonist (CHIR-99021), and Wnt inhibitor (LGK-974), each incubated for 14 days. ELISA and RT-qPCR were used to verify the protein and mRNA expression of β-catenin, LRP5 and TCF, the key factors in Wnt/β-catenin signaling pathway. The average fluorescence intensity of 3β-hydroxysteroid dehydrogenase (3β-HSD) on the surface of LCs was detected by immunofluorescence (IF) assay. The content of testosterone secreted in cell culture medium was detected by ELISA. The results of flow cytometry indicated that we successfully extracted and cultured BMSCs. Moreover, post 14 days of incubation, the changes of β-catenin, LRP5 and TCF, at the protein and mRNA level demonstrate successful intervention in the activation and inhibition of the intracellular Wnt/β-catenin signaling pathway. Compared with the control group, the LCs surface marker 3β-HSD expression intensity in the CHIR-99,021 group was significantly increased by 69% (p

Abstract Limited evidence suggests that autoimmune diseases are associated with an increased risk of cervical artery dissection (CeAD). We hypothesized individuals with systemic lupus erythematosus (SLE) would have an increased risk of CeAD following SLE diagnosis compared to matched non-lupus controls. We queried a de-identified United States electronic medical records network (TriNetX, Inc.) for individuals aged 10 and older from 2012 to 2020, for two cohorts: (1) SLE and (2) non-lupus controls, excluding those with prior CeAD. We used propensity matching to control for confounding variables and calculated the risk ratio (RR) for CeAD occurring over four years’ follow-up, secondarily exploring cumulative incidence. After matching, both cohorts contained 77,008 patients, who were mostly female (89%). The incidence and risk of CeAD was significantly greater among those with SLE compared to matched non-lupus controls [95% CI] (0.08% vs. 0.04%; RR = 2.33 [1.49;3.66]; P

Abstract Lung cancer, particularly adenocarcinoma, ranks high in morbidity and mortality rates worldwide, with a relatively low five-year survival rate. To achieve precise prognostic assessment and clinical intervention for patients, thereby enhancing their survival prospects, there is an urgent need for more accurate stratification schemes. Currently, the TNM staging system is predominantly used in clinical practice for prognostic evaluation, but its accuracy is constrained by the reliance on physician experience. Although biomarker discovery based on molecular pathology offers a new perspective for prognostic assessment, its dependence on expensive gene panel testing limits its widespread clinical application. Pathological images contain abundant diagnostic information, providing a new avenue for prognostic evaluation. In this study, we employed advanced Hover-Net technology to accurately quantify the abundance of epithelial cells, lymphocytes, macrophages, and neutrophils from pathological images, and delved into the clinical and biological significance of these cellular abundances. Our research findings reveal that, in contrast to patients classified as N0 stage, those belonging to the N1 stage demonstrated a marked elevation in the infiltration of epithelial cells, lymphocytes, macrophages, and neutrophils. Notably, the infiltration patterns of lymphocytes and neutrophils exhibited an inverse relationship with the activation status of numerous pivotal gene pathways, including the HALLMARK_HEME_METABOLISM pathway. Furthermore, our analysis distinguished FABP7 as a prognostic biomarker, exhibiting pronounced differential expression between patients with high and low levels of neutrophil infiltration, indicate that cellular abundance analysis based on pathological images can provide a more accurate and cost-effective prognostic evaluation, offering new strategies for the clinical management of lung adenocarcinoma.

Abstract Free oligosaccharides in human milk have many biological functions for infant health. The reducing end of most human milk oligosaccharides is lactose, and caprine milk was reported to contain oligosaccharides structurally similar to those present in human milk. The structures of oligosaccharides were traditionally determined using nuclear magnetic resonance spectroscopy or enzyme digestion followed by various detection methods, e.g., liquid. Mass spectrometry has much higher sensitivity than nuclear magnetic resonance spectroscopy and enzyme digestion. However, conventional mass spectrometry methods only determine part of the structures of oligosaccharides, i.e., compositions and linkage positions. In this study, we used the latest developed mass spectrometry method, namely logically derived sequence tandem mass spectrometry, to determine the complete structures (i.e., composition, linkage positions, anomericities, and stereoisomers) of free neutral trisaccharides in caprine colostrum and mature milk. The high sensitivity of mass spectrometry enables us to discover oligosaccharides of low abundance. Isomers of (Hex)2HexNAc, (Hex)3, and (Hex)2Fuc which have not been reported before were identified. Many of them do not have lactose at the reducing end. Instead, the reducing end is either Glcβ-(1–4)-Glc or Glcβ-(1–4)-GlcNAc. These unusual oligosaccharides are higher in concentration and more structurally diverse in caprine colostrum than that in caprine mature milk and human milk. The structural diversity indicates more complicated biosynthetic pathways of caprine milk compared to that of human milk.

Abstract Removal of accumulated dyes from the environment water bodies is essential to prevent further harm to humans. The development and design of new alternative nanoadsorbents that can conveniently, quickly, and efficiently improve the adsorption and removal efficiency of dyes from wastewater remains a huge challenge. An amorphous TiO2 with a magnetic core-shell-shell structure (Fe3O4@PDA@a-TiO2, denoted as FPaT) was constructed through a series of steps. The studies on the formation mechanism of FPaT indicated that the reaction temperature was the most important parameter affecting crystal structure. To analyze the magnetic properties of the core, the amorphous structure of the shell, and the surface properties (size and morphology, elemental composition, functional groups, crystal structure, magnetic properties, etc.) of FPaT, various analytical techniques including scanning electronic microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and vibrating sample magnetometer (VSM) were utilized to characterize it. Based on the unique physicochemical properties of its surface, the FPaT was applied to highly adsorb methylene blue (MB) from simulated wastewater. Furthermore, batch adsorption experiments towards MB were performed to assess the high adsorption ability and reusability of the prepared FPaT. Using 4.5 mg of FPaT to adsorb MB solution with an initial concentration of 10 mg/L (pH = 8.2), 97% adsorption rate was achieved within 30 min. Compared with the previously reported values of other absorbent materials, the maximum adsorption capacity (313.7 mg/g) is much higher. The equilibrium adsorptions and the adsorption kinetic data were better depicted by the Langmuir isothermal adsorption model (R 2 = 0.943) and by a second-order kinetic model (R 2 = 0.999), respectively. In conclusion, this work indicates that FPaT, as a novel adsorbent, has good application prospects for removing MB from actual dye wastewater.

Abstract Fear of progression (FoP) is a stressful psychosocial condition that affects health and quality of life. Breast cancer is recognized as the most prevalent cancer among women globally. This study aims to determine the prevalence of FoP, coping strategies, and associated factors among Malaysian female breast cancer survivors. A cross-sectional survey was conducted among 242 female breast cancer patients recruited from the south of Malaysia using simple random sampling method. The questionnaire captured sociodemographic characteristics, clinical factors, coping strategies and FoP level. Factors associated with FoP were investigated using multiple logistic regression analysis. The mean age was 55.1 (± 10.9) years. Majority of them were Malays, attained secondary ducation and above, married, unemployed, and in advanced cancer stages. Most patients had low FoP levels, with a smaller proportion having moderate-to-high FoP levels (10.7%). Higher education (AOR = 5.10, P = 0.050), being employed (AOR = 3.85, P = 0.020), advanced can cer stage (AOR = 4.23, P = 0.030), and adoption of avoidant coping strategy (AOR = 1.19, P = 0.009), were associated with higher FoP level. The level of FoP is low among Malaysian females with breast cancer. Higher levels of FoP were associated with higher educational levels, employment status, advanced cancer stage, and utilization of avoidant coping strategies. The fundamental cognitive process mainly affects FoP, rather than disease-related factors.

Abstract To investigate for the risk of uveitis among such patients. A retrospective cohort study utilized the TriNetX database and recruited pediatric autoimmune patients diagnosed between January 1st 2004 and December 31st 2022. The non-autoimmune cohort were randomly selected control patients matched by sex, age, and index year. The main outcome is the incidence of new-onset uveitis. 175,328 pediatric patients with autoimmune diseases (mean age 10.7 +/- 5.1 years; 55.8% female; 66.2% White) and 175,328 pediatric patients without autoimmune diseases (mean age 10.8+/- 5.1 years; 55.7% female; 66% White) were recruited. The autoimmune cohort demonstrated a significantly increased uveitis risk across our 18-year study period (HR 4.42 [95% CI 3.98–4.90]). Iridocyclitis, chorioretinal inflammation, unspecified purulent endophthalmitis, panuveitis, retinal vasculitis, and sympathetic uveitis were uveitis conditions significantly associated with autoimmune diseases. Autoimmune patients who had used immunosuppressant medications had increased uveitis risk compared to those who had never used immunosuppressants. Our subgroup analysis also demonstrated a significantly increased uveitis risk associated with specific autoimmune conditions. Conditions include inflammatory arthritis, systemic autoimmune rheumatic diseases, systemic vasculitis, inflammatory bowel disease, psoriasis, multiple sclerosis, and immune thrombocytopenic purpura. Using hazard ratios HR for comparison, we were able to identify that, out of the previously broadly defined category of autoimmune diseases, only these specific conditions were significantly associated with pediatric uveitis. Uveitis was significantly associated with autoimmune diseases among the pediatric population.

Abstract Treating metastatic brain tumors remains a significant challenge. This study introduces and applies the Patient-Derived Tumor Spheroid (PDTS) system, an ex vivo model for precision drug testing on metastatic brain tumor. The PDTS system utilizes a decellularized extracellular matrix (dECM) derived from adipose tissue, combined with the tumor cells, to form tumor spheroids. These spheroids were subsequently used to test anticancer drugs, with results compared to the clinical outcomes observed after administering these treatments to patients. To assess the validity of the data, the correlation between the drug responses observed in the PDTS model and actual patient outcomes was analyzed. Chi-square tests evaluated the significance of associations between lab predictions and clinical outcomes, using a significance threshold of p

Abstract Bone health screening is crucial before and during androgen deprivation therapy (ADT) for prostate cancer, yet changes in bone mineral density during ADT are often overlooked. To improve surveillance rates, we developed an auto-recruit path integrated into the outpatient system, where a pop-up reminder prompts physicians to arrange bone health screenings when ADT is prescribed without a dual-energy x-ray absorptiometry (DXA) screening in the past year. If selected, the system orders DXA and related examinations automatically. We retrospectively reviewed DXA screening rates from 2000 to 2018. During that period, only 286 out of 3,019 patients (9.5%) received DXA screenings. After implementing the auto-recruit system, 251 out of 747 eligible patients (33.6%) were screened from March 2021 to February 2022. Participants using ADT for over a year had worse T-scores and higher osteoporosis rates (34.5% vs. 23.2%) compared to those using ADT for less than a year. Post-screening, there was a significant increase in calcium supplement and bone protective agent use, highlighting improved patient awareness and proactive bone health management. In conclusion, bone health screening for prostate cancer patients on ADT remains an unmet need. The auto-recruit path in the outpatient system effectively increases screening rates and enhances bone health management.

Abstract Tongue cancer is among the most prevalent head and neck cancers and is most commonly treated via surgery. We assessed the articulation differences in patients with early and advanced tongue cancer. The study included 26 postoperative tongue cancer patients. We evaluated articulation based on bilabial, labiodental, apical, posterior, laminal, apical front, and apical back speech sounds. The 26 postoperative tongue cancer patients (24 males, two females) had an average age of 54.3 (range 37–89 old) years. Twelve patients were classified as early T stage (T1/T2), while 14 were classified as advanced T stage (T3/T4). The total articulation score was not significantly related to the T stage but apical sounds were so associated. The total articulation score did not significantly differ between postoperative patients with early and advanced tongue cancer. In subgroup analysis, the apical sound was significantly impaired in postoperative patients with advanced tongue cancer.

Abstract Chronic hepatitis B (CHB) leads to liver inflammation and dysfunction, resulting in liver fibrosis and cancer. Nucleos(t)ide analogues (NAs), inhibitors of hepatitis B virus (HBV), specifically suppress HBV replication. We proposed that immune modulation benefits seroconversion by HBsAg loss. However, activation of T lymphocytes also deteriorates hepatic inflammation. Therefore, we intended to investigate the T cell status and its relationship with hepatic functions in CHB patients treated with NAs. Serum markers, including liver function markers AST, ALT, and HBV-infected markers HBV DNA, HBsAg, HBeAg, and HBsAb were measured in the clinical routine. The T cell levels and markers, including CD69, CD107a, CXCR3, and PD-1 were investigated using flow cytometry. Meanwhile, IFNγ, IL-2, and CXCL10 as immune activation markers in the PBMCs were investigated using qPCR. To validate the effects of NAs on T cell status, qPCR and flow cytometry were used to investigate the gene expression in the HepG2 and PLC5 cells treated with NAs, and in the healthy PBMCs treated with the cell-cultured supernatant. We found that NAs significantly suppressed HBV DNA and reduced AST and ALT levels in the CHB patients. Meanwhile, AST and ALT were both positively correlated with activation marker CD107a in CD8+ T cells. In addition, we found that the CHB patients with seroconversion exhibited a higher CD4/CD8 ratio (p

Abstract This study aimed to evaluate the effect of Astragalus polysaccharides (PG2) on reducing chemotherapy-induced fatigue (CIF) and toxicity, thereby encouraging compliance to chemotherapy. This was a randomized, placebo-controlled, phase 2 study. Patients with stage II/III early breast cancer planning to undergo adjuvant anthracycline-based chemotherapy were randomly assigned to receive PG2 500 mg or placebo on days 1, 3, and 8 every 21 days. The fatigue global score (FGS) was assessed using the brief fatigue inventory (BFI)-Taiwan. The Breast Cancer-Specific Module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Core30 evaluated the health-related quality of life during the first four cycles of adjuvant chemotherapy. Overall, 66 eligible patients were equally randomized into the PG2 and placebo groups between March 01, 2018, and March 09, 2021. The mean change in the FGS and fatigue intensity did not significantly differ between both groups. However, the FGS and fatigue intensity were less aggravated in the first four cycles in the premenopausal-PG2 group than in the placebo group. Our study concluded PG2 combined with adjuvant chemotherapy can reduce CIF, insomnia, the negative effect on future perspectives, and improve global health status, especially for premenopausal patients with breast cancer. Trial registration number: NCT03314805 registered on 19/10/2017.

Abstract Ice wine is produced from concentrated grape juice obtained by the natural freezing and pressing of grapes. The high sugar content of this juice has an impact on fermentation. To investigate the impact of the initial sugar concentration on the fermentation of ice wine, the initial sugar concentration of Vidal ice grape juice was adjusted to 370, 450, 500 and 550 g/L by the addition of glucose. The fermentation process was conducted at a temperature of 18 °C with Zymaflore ST yeast. To ensure optimal fermentation, the yeast assimilable nitrogen (YAN) in the grape juice was adjusted to 350 mg/L using a commercial nitrogen source. The initial sugar concentrations (370, 450, 500, and 550 g/L) were significantly negatively correlated with the number of viable yeast during active fermentation, the total consumption of sugar and YAN, and ethanol production (130.26, 117.83, 106.14, and 90.85 g/L) but positively correlated with the production of acetic acid (0.82–2.86 g/L) and acetaldehyde. Fermentation with initial sugar concentrations ≥ 500 g/L (500 and 550 g/L) produced ethanol (106.14 and 90.85 g/L) and excessive acetic acid (2.14 and 2.86 g/L), inhibited the esterification of n-butanol and n-hexanol, and promoted the production of isopentanol, isoamyl acetate, diethyl succinate, ethyl hexanoate and ethyl octanoate while increasing the production of 2-phenylethanol and isobutanol. The initial sugar concentration affected the production of glycerol, isobutanol, ethyl acetate, and diethyl succinate, but it did not affect the final contents of the ice wine. This study examined fermentation dynamics, including substrate consumption, yeast cell production, and the production of important metabolites such as ethanol, acetic acid, higher alcohols, and esters. Appropriate initial concentrations of YAN and sugar (below 500 g/L) and a relatively high ratio of glucose to fructose (between 1:1 and 1.7:1) is preferable for effective ice wine fermentation.

Abstract Physical activity (PA) and fruit and vegetable consumption (FVC) are crucial factors jointly affecting young adults’ physical and mental health. However, the psychosocial interactive mechanisms of these behaviors remain understudied. Using a two-wave prospective design over two months, this study investigated the psychological mechanisms underlying multiple health behavior change (MHBC) through a novel two-layer social-cognitive framework, the Compensatory Carry-Over Action Model (CCAM), among 322 Chinese college students (19.47 ± 0.99 years; 55.6% female). Structural equation modeling with path analysis was conducted using Mplus 8.8 for data analysis. Results indicated an acceptable model fit for the hypothesized model, with χ 2 = 120.845, df = 41, χ 2/df = 2.947, CFI = 0.940, TLI = 0.901, RMSEA = 0.078 [90% CI = 0.062 to 0.094], and SRMR = 0.079. The model explained 54.9% and 50.0% of the variance in PA and FVC, respectively. In the first layer, focusing on the individual behavior change process, both volitional self-efficacy and planning were identified as significant mediators in the intention-behavior relationship for PA and FVC (indirect effects = 0.03 to 0.14, all p .05). However, volitional self-efficacy and planning played a significant mediating role in the interaction between PA/FVC intention and FVC/PA behavior (indirect effects = 0.01 to 0.04, all p

Abstract In recent years, the hydroacoustic communication MAC (Medium Access Control) protocol has attracted wide attention. Hydroacoustic communication networks suffer from issues such as long propagation delays and rapid dynamic changes in network load, which prevent the maximization of network performance through the use of a single transmission mode. In this paper, we propose a Dynamic Switching Transmission MAC protocol called the DSTM-MAC protocol. Firstly, the protocol realizes the design of dynamic switching transmission mode by adapting to changes in network load, introduces a more accurate model for total system delay, and computes parameters such as the switching threshold L and the optimal fixed contention window. Secondly, it carries out parameter design for different transmission modes and realizes dynamic concurrent transmission based on these modes, ultimately achieving the goal of maximizing network performance improvement. Finally, experiments demonstrate that the DSTM-MAC protocol surpasses the traditional DCF protocol in terms of end-to-end delay and system throughput.

Abstract To investigate the effects of early-onset sepsis (EOS) on retinopathy of prematurity (ROP) in extremely premature infants (EPIs) by using propensity score matching (PSM). Clinical data of 591 EPIs admitted to NICU, Senior Department of Pediatric, PLA General Hospital from May 1, 2015 to May 1, 2022 were retrospectively analyzed. They were divided into an EOS group and a non-EOS group according to whether they had confirmed EOS or not. The incidence of ROP and severe ROP was compared between the two groups using the 1:1 PSM method. Of the 591 EPIs, 57 (9.6%) fell in the EOS group and the remaining 534 in the non-EOS group. There were statistical differences in artificial conception, cesarean section, bronchopulmonary dysplasia, duration of invasive mechanical ventilation, days of oxygen use, amniotic fluid contamination, and premature rupture of membranes between the two groups (all P 0.05). Of the 57 cases in the EOS group, 51 were successfully matched, in which the incidence of severe ROP was higher than that in the non-EOS group [47.1% (24/51) vs. 27.5% (14/51), OR 2.349,95% CI 1.030 to 5.360, P 0.05]. EOS didn’t seem to increase the incidence of ROP in EPIs, but was associated with an increase in the degree of ROP lesions. The progression of fundus lesions in EPIs with EOS during hospitalization should be closely monitored.

Abstract Resolvin D1 (RvD1) is an endogenous anti-inflammatory mediator that modulates the inflammatory response and promotes inflammation resolution. RvD1 has demonstrated neuroprotective effects in various central nervous system contexts; however, its role in the pathophysiological processes of intracerebral hemorrhage (ICH) and the potential protective mechanisms when combined with exercise rehabilitation remain unclear. A mouse model of ICH was established using collagenase, and treatment with RvD1 combined with three weeks of exercise rehabilitation significantly improved neurological deficits, muscle strength, learning, and memory in ICH mice while reducing anxiety-like behavior. RvD1 combined with exercise rehabilitation upregulated anti-inflammatory factors, inhibited the inflammatory state, and activated the BDNF/TrkB/PI3K/AKT pathway. TUNEL staining confirmed a decrease in residual apoptotic neurons, while transmission electron microscopy showed an increase in mitochondrial autophagosomes with combined treatment. Mendelian randomization and molecular docking further confirmed the association of RvD1 with targets related to mitophagy and inflammatory factors, clarifying the mechanism of RvD1 involvement. In summary, RvD1 combined with exercise rehabilitation activates the BDNF/TrkB/PI3K/AKT signaling pathway, effectively reduces neuronal apoptosis and inflammatory responses following ICH in mice, and participates in mitochondrial autophagy-related states. This comprehensive therapeutic strategy promotes neurological recovery and provides insights for clinical management of this condition.

Abstract Accurate characterisation of seismic source mechanisms in mining environments is crucial for effective hazard mitigation, but it is complicated by the presence of anisotropic geological conditions. Neglecting anisotropic effects during moment tensor (MT) inversion introduces significant distortions in the retrieved source characteristics. In this study, we investigated the impact of ignoring anisotropy during MT inversion on the reliability of hazard assessment. We investigated a high-energy (2.18 $$\times$$ 106 J) induced by mining activities in the Nantun coal mine in China. The subsurface was modelled as a vertically transversely isotropic medium, incorporating four different levels of anisotropy derived from site-specific geological and tomographic data. The results demonstrate that neglecting anisotropy led to significant distortions in the retrieved source parameters, including polarity flips and the introduction of spurious non-double-couple components. These artefacts compromised the accuracy of hazard analysis and undermined the effectiveness of risk management strategies. In contrast, the sequential inversion method yields a MT solution with a 0.14 misfit, accurately retrieving the focal mechanism, which is interpreted as a normal right-lateral oblique shear failure along the F3 fault. This study highlights the importance of properly incorporating anisotropy effects when analysing induced seismicity in heterogeneous mining environments. The use of a homogeneous Green’s function for MT inversion may be inadequate for reliable hazard assessment, underscoring the need for advanced techniques that can effectively model the influence of subsurface anisotropy on seismic wave propagation and source retrieval.

Abstract Hospital-acquired infections (HAIs) are serious complication for patients with acute ischemic stroke (AIS), often resulting in poor functional outcomes. However, no existing model can specifically predict HAI in AIS patients. Therefore, we employed the Gradient Boosting matching learning algorithm to establish predictive models for HAI occurrence in AIS patients and poor 30-day functional outcomes (modified Rankin Scale > 2) in AIS patients with HAI by analyzing electronic health records from 6560 AIS patients. Model performance was evaluated through internal cross-validation and external validation using an independent cohort of 3521 AIS patients. The established models demonstrated robust predictive performance for HAI in AIS patients, achieving area under the receiver operating characteristic curves (AUROCs) of 0.857 ± 0.008 during internal validation and 0.825 ± 0.002 during external validation. For AIS patients with HAI, the second model effectively predict poor 30-day functional outcomes, with AUROCs of 0.905 ± 0.009 during internal validation and 0.907 ± 0.002 during external validation. In conclusion, machine learning models effectively identify the HAI occurrence and predict poor 30-day functional outcomes in AIS patients with HAI. Future prospective studies are crucial for validating and refining these models for clinical application, as well as for developing an accessible flowchart or scoring system to enhance clinical practices.

Abstract As an alternative to assessments performed by human experts, artificial intelligence (AI) is currently being used for screening fundus images and monitoring diabetic retinopathy (DR). Although AI models can provide quasi-clinician diagnoses, they rarely offer new insights to assist clinicians in predicting disease prognosis and treatment response. Using longitudinal retinal imaging data, we developed and validated a predictive model for DR progression: AI-driven Diabetic Retinopathy Progression Prediction Algorithm (ADRPPA). In this retrospective study, we analyzed paired retinal fundus images of the same eye captured at ≥ 1-year intervals. The analysis was performed using the EyePACS dataset. By analyzing 12,768 images from 6384 eyes (2 images/eye, taken 733 ± 353 days apart), each annotated with DR severity grades, we trained the neural network ResNeXt to automatically determine DR severity. EyePACS data corresponding to 5108 (80%), 639 (10%), and 637 (10%) eyes were used for model training, validation, and testing, respectively. We further used an independent e-ophtha dataset comprising 148 images annotated with microaneurysms, 118 (75%) and 30 (25%) of which were used for training and validation, respectively. This dataset was used to train the neural network Mask Region–based Convolutional Neural Network (Mask-RCNN) for quantifying microaneurysms. The DR and microaneurysm scores from the first nonreferable DR (NRDR) image of each eye were used to predict progression to referable DR (RDR) in the second image. The area under the receiver operating characteristic curve values indicating our model’s performance in diagnosing RDR were 0.963, 0.970, 0.968, and 0.971 for the trained ResNeXt models with input image resolutions of 256 × 256, 512 × 512, 768 × 768, and 1024 × 1024 pixels, respectively. In the validation of the Mask-RCNN model trained on the e-ophtha dataset resized to 1600 pixels in height, the recall, precision, and F1-score values for detecting individual microaneurysms were 0.786, 0.615, and 0.690, respectively. The best model combination for predicting NRDR-to-RDR progression included the 768-pixel ResNeXt and 1600-pixel Mask-RCNN models; this combination achieved recall, precision, and F1-scores of 0.338 (95% confidence interval [CI]: 0.228–0.451), 0.561 (95% CI: 0.405–0.714), and 0.422 (95% CI: 0.299–0.532), respectively. Thus, deep learning models can be trained on longitudinal retinal imaging data to predict NRDR-to-RDR progression. Furthermore, DR and microaneurysm scores generated from low- and high-resolution fundus images, respectively, can help identify patients at a high risk of NRDR, facilitating timely treatment.