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Abstract Background Myopia is one of the most common eye diseases in children and adolescents worldwide, and scleral remodeling plays a role in myopia progression. However, the identity of the initiating factors and signaling pathways that induce myopia-associated scleral remodeling is still unclear. This study aimed to identify biomarkers of scleral remodeling to elucidate the pathogenesis of myopia. Methods The gene expression omnibus (GEO) and comparative toxicogenomics database (CTD) mining were used to identify the miRNA-mRNA regulatory network related to scleral remodeling in myopia. Real-time quantitative PCR (RT-qPCR), Western blot, immunofluorescence, H&E staining, Masson staining, and flow cytometry were used to detect the changes in the FOXO signaling pathway, fibrosis, apoptosis, cell cycle, and other related factors in scleral remodeling. Results miR-15b-5p/miR-379-3p can regulate the FOXO signaling pathway. Confirmatory studies confirmed that the axial length of the eye was significantly increased, the scleral thickness was thinner, the levels of miR-15b-5p, miR-379-3p, PTEN, p-PTEN, FOXO3a, cyclin-dependent kinase (CDK) inhibitor 1B (CDKN1B) were increased, and the levels of IGF1R were decreased in Len-induced myopia (LIM) group. CDK2, cyclin D1 (CCND1), and cell cycle block assessed by flow cytometry indicated G1/S cell cycle arrest in myopic sclera. The increase in BAX level and the decrease in BCL-2 level indicated enhanced apoptosis of the myopic sclera. In addition, we found that the levels of transforming growth factor-β1 (TGF-β1), collagen type 1 (COL-1), and α-smooth muscle actin (α-SMA) were decreased, suggesting scleral remodeling occurred in myopia. Conclusions miR-15b-5p/miR-379-3p can regulate the scleral cell cycle and apoptosis through the IGF1R/PTEN/FOXO signaling pathway, thereby promoting scleral remodeling in myopia progression. Graphical Abstract

Background/Aims Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P

Background/Aims Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection. Methods Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days. Results A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were –2.9, –3.3, –3.5 and –0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was –2.9, –2.4, –2.0, and –0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths. Conclusions In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.

Abstract Ulcerative colitis (UC) is an idiopathic, chronic inflammatory condition of the colon, characterized by repeated attacks, a lack of effective treatment options, and significant physical and mental health complications for patients. The endoplasmic reticulum (ER) is a vital intracellular organelle in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is induced when the body is exposed to adverse external stimuli. Numerous studies have shown that ERS-induced apoptosis plays a vital role in the pathogenesis of UC. Mogroside V (MV), an active ingredient of Monk fruit, has demonstrated excellent anti-inflammatory and antioxidant effects. In this study, we investigated the therapeutic effects of MV on dextran sulfate sodium (DSS)-induced UC and its potential mechanisms based on ERS. The results showed that MV exerted a protective effect against DSS-induced UC in mice as reflected by reduced DAI scores, increased colon length, reduced histological scores of the colon, and levels of pro-inflammatory cytokines, as well as decreased intestinal permeability. In addition, the expression of ERS pathway including BIP, PERK, eIF2α, ATF4, CHOP, as well as the apoptosis-related protein including Caspase-12, Bcl-2 and Bax, was found to be elevated in UC. However, MV treatment significantly inhibited the UC and reversed the expression of inflammation signaling pathway including ERS and ERS-induced apoptosis. Additionally, the addition of tunicamycin (Tm), an ERS activator, significantly weakened the therapeutic effect of MV on UC in mice. These findings suggest that MV may be a therapeutic agent for the treatment of DSS-induced UC by inhibiting the activation of the ERS-apoptosis pathway, and may provide a novel avenue for the treatment of UC.

Rationale & Objective: The development of anuria has been linked to worse clinical outcomes in patients undergoing peritoneal dialysis (PD). Our objective was to investigate the incidence, risk factors, and associated clinical outcomes of anuria within the first year after starting PD. Study Design: Retrospective cohort study. Setting & Participants: Patients who started continuous ambulatory peritoneal dialysis at our center between 2006 and 2020 were included and followed up until January 31, 2023. Exposure: Age, sex, diabetes, temporary hemodialysis, angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs), diuretics, baseline urine volume, serum albumin, daily glucose exposure, peritonitis, and incremental PD. Outcomes: The primary outcome was early anuria, defined as 24-hour urine volume ≤100 mL within the first year of PD initiation. Secondary outcomes included all-cause mortality, cardiovascular disease mortality, technique failure, and peritonitis. Analytical Approach: Cox proportional hazards model. Results: A total of 2,592 patients undergoing continuous ambulatory peritoneal dialysis aged 46.7 ± 14.9 years were recruited. Among them, 58.9% were male, and 24.0% had diabetes. Within the first year of PD therapy, 159 (6.13%) patients developed anuria, with a median duration of 7.53 (interquartile range, 3.93-10.0) months. Higher baseline urine volume (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.90-0.97), higher serum albumin (HR, 0.92; 95% CI, 0.88-0.95), having diabetes before PD (HR, 0.57; 95% CI, 0.35-0.92), and prescribed incremental PD (HR, 0.27; 95% CI, 0.14-0.51) were associated with a reduced risk for early anuria, whereas a higher level of daily glucose exposure (HR, 1.01; 95% CI, 1.00-1.01) was identified as a risk factor for early anuria. Subgroup analyses showed that using ACEis or ARBs was linked to a lower risk of early anuria (HR, 0.25; 95% CI, 0.09-0.69) in diabetic patients. Treating early anuria as a time-dependent covariate, early anuria was associated with a higher risk for all-cause mortality (HR, 1.69; 95% CI, 1.23-2.32) and technique failure (HR, 1.43; 95% CI, 1.00-2.04) after adjusting for confounding factors. Limitations: Single-center and observational study. Conclusions: Among PD patients at a single center in China, early anuria was relatively uncommon but associated with an increased risk of mortality and PD technique failure. Incremental PD, higher baseline urine output and serum albumin, and lower daily glucose exposure were associated with a lower risk of early anuria. Clinical trials are needed to evaluate the optimal PD techniques to preserve residual kidney function and maximaze outcomes. Plain-Language Summary: The development of anuria has been linked to worse clinical outcomes in patients undergoing peritoneal dialysis (PD). However, does the development of early anuria, which is defined as 24-hour urine volume ≤100 mL, within the first year after PD initiation influence the clinical outcomes of these patients? What are the predictors of early anuria? We conducted a single-center retrospective cohort study and found lower baseline urine volume, lower serum albumin, full-dose PD start, absence of diabetes mellitus, higher daily glucose exposure, and in patients with diabetes mellitus, non-use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers were associated with early anuria. Early anuria was related to a higher risk for all-cause mortality and technique failure. The results provide information for optimizing patient care and improving the prognosis of patients undergoing PD.

Abstract Alzheimer's disease (AD) is the most common age‐related neurodegenerative disorder leading to cognitive decline. Excessive cytosolic calcium (Ca2+) accumulation plays a critical role in the pathogenesis of AD since it activates the NOD‐like receptor family, pyrin domain containing 3 (NLRP3), switches the endoplasmic reticulum (ER) unfolded protein response (UPR) toward proapoptotic signaling and promotes Aβ seeding. Herein, a liposomal nanodrug (felodipine@LND) is developed incorporating a calcium channel antagonist felodipine for Alzheimer's disease treatment through a low‐intensity pulse ultrasound (LIPUS) irradiation‐assisted blood brain barrier (BBB)‐crossing drug delivery. The multifunctional felodipine@LND is effectively delivered to diseased brain through applying a LIPUS irradiation to the skull, which resulted in a series of positive effects against AD. Markedly, the nanodrug treatment switched the ER UPR toward antioxidant signaling, prevented the surface translocation of ER calreticulin (CALR) in microglia, and inhibited the NLRP3 activation and Aβ seeding. In addition, it promoted the degradation of damaged mitochondria via mitophagy, thereby inhibiting the neuronal apoptosis. Therefore, the anxiety‐like behavior and cognitive impairment of 5xFAD mice with AD is significantly ameliorated, which manifested the potential of LIPUS – assisted BBB‐crossing delivery of felodipine@LND to serve as a paradigm for AD therapy based on the well‐recognized clinically available felodipine.

ObjectiveTo mine and analyze adverse events (AEs) related to proteasome inhibitors in multiple myeloma based on the FDA Adverse Event Reporting System (FAERS), providing references for rational clinical medication.MethodsAE data related to multiple myeloma proteasome inhibitors were collected from the FAERS from the first quarter of 2010 to the first quarter of 2024. Signal mining of AEs was conducted using the reporting odds ratio method and Bayesian confidence propagation neural network method.ResultsA total of 8,805 reports for bortezomib, 5,264 for carfilzomib, and 8,771 for ixazomib were collected, with corresponding AE signals of 474, 279, and 287, respectively, involving 23, 21, and 22 System Organ Classes (SOCs). The report information for the three drugs tended to be consistent: more cases were reported in males than in females; the majority of patients were 65 years and over; AEs mostly occurred within 6 months of medication; the outcomes primarily consisted of hospitalization, prolonged hospital stay, and other serious adverse events; the primary reporting country was the United States. The most affected SOCs were infections and infestations, general disorders and administration site conditions, and blood and lymphatic system disorders.ConclusionThe overall distribution of AEs for the three multiple myeloma proteasome inhibitors was consistent, but there were certain differences in specific AE signal characteristics, which should be noted in clinical applications.

The blood supply in the retina ensures photoreceptor function and maintains regular vision. Leber's hereditary optic neuropathy (LHON), caused by the mitochondrial DNA mutations that deteriorate complex I activity, is characterized by progressive vision loss. Although some reports indicated retinal vasculature abnormalities as one of the comorbidities in LHON, the paracrine influence of LHON-affected retinal ganglion cells (RGCs) on vascular endothelial cell physiology remains unclear. To address this, we established an in vitro model of mitochondrial complex I deficiency using induced pluripotent stem cell-derived RGCs (iPSC-RGCs) treated with a mitochondrial complex I inhibitor rotenone (Rot) to recapitulate LHON pathologies. The secretomes from Rot-treated iPSC-RGCs (Rot-iPSC-RGCs) were collected, and their treatment effect on human umbilical vein endothelial cells (HUVECs) was studied. Rot induced LHON-like characteristics in iPSC-RGCs, including decreased mitochondrial complex I activity and membrane potential, and increased mitochondrial reactive oxygen species (ROS) and apoptosis, leading to mitochondrial dysfunction. When HUVECs were exposed to conditioned media (CM) from Rot-iPSC-RGCs, the angiogenesis of HUVECs was suppressed compared to those treated with CM from control iPSC-RGCs (Ctrl-iPSC-RGCs). Angiogenesis-related proteins were altered in the secretomes from Rot-iPSC-RGC-derived CM, particularly angiopoietin, MMP-9, uPA, collagen XVIII, and VEGF were reduced. Notably, GeneMANIA analysis indicated that VEGFA emerged as the pivotal angiogenesis-related protein among the identified proteins secreted by health iPSC-RGCs but reduced in the secretomes from Rot-iPSC-RGCs. Quantitative real-time PCR and western blots confirmed the reduction of VEGFA at both transcription and translation levels, respectively. Our study reveals that Rot-iPSC-RGCs establish a microenvironment to diminish the angiogenic potential of vascular cells nearby, shedding light on the paracrine regulation of LHON-affected RGCs on retinal vasculature.

Radiation-induced lung injury (RILI) is a severe complication arising from thoracic tumor radiotherapy, which constrains the possibility of increasing radiation dosage. Current RILI therapies provide only limited relief and may result in undesirable side effects. Therefore, there is an urgent demand for effective and low-toxicity treatments for RILI. Macrophages play a pivotal role in RILI, promoting inflammation in the initial stages and facilitating fibrosis in the later stages. Sodium clodronate, a bisphosphonate, can induce macrophage apoptosis when encapsulated in liposomes. In this study, we explored the potential of liposomal sodium clodronate (LC) as a specific agent for depleting macrophages to alleviate acute RILI. We assessed the impact of LC on macrophage consumption both in vitro and in vivo. In a mouse model of acute RILI, LC treatment group led to a reduction in alveolar macrophage counts, mitigated lung injury severity, and lowered levels of pro-inflammatory cytokines in both plasma and bronchoalveolar lavage fluid. Additionally, we further elucidated the specific effects and mechanism of LC on macrophages in vitro. Alveolar macrophages MHS cells were subjected to varying concentrations of LC (0, 50, 100, 200 μg/ml), and the results demonstrated its dose-dependent inhibition of cell proliferation and induction of apoptosis. Moreover, LC decreased the secretion of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Conditioned media from LC-treated macrophages protected alveolar epithelial cells MLE-12 from radiation-induced damage, as demonstrated by reduced apoptosis and DNA damage. These findings imply that LC-mediated macrophage depletion may present a promising therapeutic strategy for alleviating radiation-induced lung injury.

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

In neurodegenerative diseases, proteins fold into amyloid structures with distinct conformations (strains) that are characteristic of different diseases. However, there is a need to rapidly identify amyloid conformations in situ. Here, we use machine learning on the full information available in fluorescent excitation/emission spectra of amyloid-binding dyes to identify six distinct different conformational strains in vitro, as well as amyloid-β (Aβ) deposits in different transgenic mouse models. Our EMBER (excitation multiplexed bright emission recording) imaging method rapidly identifies conformational differences in Aβ and tau deposits from Down syndrome, sporadic and familial Alzheimer's disease human brain slices. EMBER has in situ identified distinct conformational strains of tau inclusions in astrocytes, oligodendrocytes, and neurons from Pick's disease. In future studies, EMBER should enable high-throughput measurements of the fidelity of strain transmission in cellular and animal neurodegenerative diseases models, time course of amyloid strain propagation, and identification of pathogenic versus benign strains.

Abstract Introduction Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). Methods The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. Results A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. Conclusion Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

Abstract The development of nanomaterials for delivering natural compounds has emerged as a promising approach for atherosclerosis therapy. However, premature drug release remains a challenge. Here, we present a ROS-responsive biomimetic nanocomplex co-loaded with Geniposide (GP) and Emodin (EM) in nanoliposome particles (LP NPs) for targeted atherosclerosis therapy. The nanocomplex, hybridized with the macrophage membrane (Møm), effectively evades immune system clearance and targets atherosclerotic plaques. A modified thioketal (TK) system responds to ROS-rich plaque regions, triggering controlled drug release. In vitro, the nanocomplex inhibits endothelial cell apoptosis and macrophage lipid accumulation, restores endothelial cell function, and promotes cholesterol effluxion. In vivo, it targets ROS-rich atherosclerotic plaques, reducing plaque area ROS levels and restoring endothelial cell function, consequently promoting cholesterol outflow. Our study demonstrates that ROS-responsive biomimetic nanocomplexes co-delivering GP and EM exert a synergistic effect against endothelial cell apoptosis and lipid deposition in macrophages, offering a promising dual-cell therapy modality for atherosclerosis regression.

Abstract The successful reprogramming of impaired wound healing presents ongoing challenges due to the impaired tissue microenvironment caused by severe bacterial infection, excessive oxidative stress, as well as the inappropriate dosage timing during different stages of the healing process. Herein, a dual-layer hydrogel with sodium alginate (SA)-loaded zinc oxide (ZnO) nanoparticles and poly(N-isopropylacrylamide) (PNIPAM)-loaded Cu5.4O ultrasmall nanozymes (named programmed time-released multifunctional hydrogel, PTMH) was designed to dynamically regulate the wound inflammatory microenvironment based on different phases of wound repairing. PTMH combated bacteria at the early phase of infection by generating reactive oxygen species through ZnO under visible-light irradiation with gradual degradation of the lower layer. Subsequently, when the upper layer was in direct contact with the wound tissue, Cu5.4O ultrasmall nanozymes were released to scavenge excessive reactive oxygen species. This neutralized a range of inflammatory factors and facilitated the transition from the inflammatory phase to the proliferative phase. Furthermore, the utilization of Cu5.4O ultrasmall nanozymes enhanced angiogenesis, thereby facilitating the delivery of oxygen and nutrients to the impaired tissue. Our experimental findings indicate that PTMHs promote the healing process of diabetic wounds with bacterial infection in mice, exhibiting notable antibacterial and anti-inflammatory properties over a specific period of time.

Abstract The violent goods vibration during curve negotiation is a huge threat to the vehicle running safety. Qualified load restraint assemblies that can significantly suppress the cargo vibration are necessary. This study proposes a novel method for evaluating the essential restraint strength, focusing on the relative motion between cargo and wagon. In the beginning, as a comparison, current methods are used to calculate the necessary stiffness of lashings, which are adopted to restrain the cargo vibration on the wagon. Based on the data of the field test, the accuracy of the established wagon-cargo coupled dynamics model is validated. The loaded wagon model negotiates the curve under different running and loading conditions. The simulation results and analysis demonstrate effective strategies for suppressing the vibration of the cargo and reveal the necessary lashing stiffness. The comparison among the results of different evaluation methods shows that the stability of the cargo can be improved by optimizing the lashing stiffness with the method of dynamics simulations. We hope this study will make a positive contribution to the safety of railway freight transportation.

Abstract Background To gain insight into the real-life care of patients in the healthcare system, data from hospital information systems and insurance systems are required. Consequently, linking clinical data with claims data is necessary. To ensure their syntactic and semantic interoperability, the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) from the Observational Health Data Sciences and Informatics (OHDSI) community was chosen. However, there is no detailed guide that would allow researchers to follow a generic process for data harmonization, i.e. the transformation of local source data into the standardized OMOP CDM format. Thus, the aim of this paper is to conceptualize a generic data harmonization process for OMOP CDM. Methods For this purpose, we conducted a literature review focusing on publications that address the harmonization of clinical or claims data in OMOP CDM. Subsequently, the process steps used and their chronological order as well as applied OHDSI tools were extracted for each included publication. The results were then compared to derive a generic sequence of the process steps. Results From 23 publications included, a generic data harmonization process for OMOP CDM was conceptualized, consisting of nine process steps: dataset specification, data profiling, vocabulary identification, coverage analysis of vocabularies, semantic mapping, structural mapping, extract-transform-load-process, qualitative and quantitative data quality analysis. Furthermore, we identified seven OHDSI tools which supported five of the process steps. Conclusions The generic data harmonization process can be used as a step-by-step guide to assist other researchers in harmonizing source data in OMOP CDM.

To reveal the dynamic mechanical characteristics of deep rocks, a series of impact tests under triaxial static stress states corresponding to depths of 300–2400 m were conducted. The results showed that both the strain rates and the stress environments in depth significantly affect the mechanical characteristics of rocks. The sensitivity of strain rate to the dynamic strength and deformation modulus shows a negative correlation with depth, indicating that producing penetrative cracks in deep environments is more difficult when damage occurs. The dynamic strength shows a tendency to decrease and then increase slightly, but decreases sharply finally. Transmissivity demonstrates a similar trend as that of strength, whereas reflectivity indicates the opposite trend. Furthermore, two critical depths with high dynamically induced hazard possibilities based on the China Jinping Underground Laboratory (CJPL) were proposed for deep engineering. The first critical depth is 600–900 m, beyond which the sensitivity of rock dynamic characteristics to the strain rate and restraint of circumferential stress decrease, causing instability of surrounding rocks under axial stress condition. The second one lies at 1500–1800 m, where the wave impedance and dynamic strength of deep surrounding rocks drop sharply, and the dissipation energy presents a negative value. It suggests that the dynamic instability of deep surrounding rocks can be divided into dynamic load dominant and dynamic load induced types, depending on the second critical depth.

The Public-Private Partnerships (PPP) financability is influenced by both internal and external factors of the project. Given the myriad of factors that influence the participation of social capital in PPP projects, in this study, we examine 14,038 PPP projects from the China Public‒Private Partnership Centre (CPPPC) database. We aim to construct an ensemble learning-based prediction model for the financability of PPP project by selecting 61 feature variables across four dimensions, namely, project characteristics, local government, the market environment, and macroeconomics. The experimental results demonstrate that the dragonfly algorithm effectively improves model prediction accuracy through the reduction of feature dimensionality. From a feature combination perspective, the combinations related to the project itself, local government, and macroeconomic factors exhibit superior predictive performance than other combinations. Among the relevant factors, the project's intrinsic characteristics exert the most significant impact on social capital participation in PPPs, followed by local government factors. Notably, the inclusion of market environment variables tends to decrease the level of model accuracy, except when considering the project's intrinsic characteristics in isolation. Thus, a dynamic approach is recommended to capturing instantaneous variables such as the market environment is recommended for enhancing model performance. Additionally, social capital should rely on an assessment of the financial capacity of local governments to ensure effective PPP outcomes.