bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical features and outcomes in kidney transplant recipients with COVID-19 pneumonia: a single center retrospective cohort study
Authors: Xu Liang , Chen Xiuxiu , Yang Xuying , Chen Song , Yang Meng , Yuan Zehua , Chen Rentian , Wang Jianli , Jiang Hongtao , Xu Jian , Wang Yi 
Published: August 2024

ObjectiveThis retrospective cohort study aimed to assess the clinical features, treatment outcomes, and short-term prognosis in kidney transplant recipients (KTRs) with concurrent coronavirus disease 2019 (COVID-19) pneumonia.MethodsKTRs with COVID-19 pneumonia who were admitted to our hospital from December 28, 2022, to March 28, 2023 were included in the study. Their clinical symptoms, responses to antiviral medications, and short-term prognosis were analyzed.ResultsA total of 64 KTRs with initial diagnosis of COVID-19 pneumonia were included in this study. The primary symptoms were fever, cough, and myalgia, with an incidence of 79.7%, 89.1%, and 46.9%, respectively. The administration of antiviral drugs (paxlovid or molnupiravir) within 1–5 days and for over 5 days demonstrated a statistically significant reduction in viral shedding time compared to the group without antiviral medication (P=0.002). Both the paxlovid and molnupiravir treatment groups exhibited a significantly shorter duration of viral shedding time in comparison to the group without antiviral drugs (P=0.002). After 6 months of recovery, there was no significantly negative impact on transplant kidney function (P=0.294).ConclusionFever, cough, and myalgia remain common initial symptoms of concurrent COVID-19 pneumonia in KTRs. Early use of antiviral drugs (paxlovid or molnupiravir) is associated with better therapeutic outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a limited impact on the short-term renal function of the KTRs with concurrent moderate or severe COVID-19 pneumonia.
Cardiac ultrasound simulation for autonomous ultrasound navigation
Authors: Amadou Abdoul Aziz , Peralta Laura , Dryburgh Paul , Klein Paul , Petkov Kaloian , Housden R. James , Singh Vivek , Liao Rui , Kim Young-Ho , Ghesu Florin C. , Mansi Tommaso , Rajani Ronak , Young Alistair , Rhode Kawal 
Published: August 2024

IntroductionUltrasound is well-established as an imaging modality for diagnostic and interventional purposes. However, the image quality varies with operator skills as acquiring and interpreting ultrasound images requires extensive training due to the imaging artefacts, the range of acquisition parameters and the variability of patient anatomies. Automating the image acquisition task could improve acquisition reproducibility and quality but training such an algorithm requires large amounts of navigation data, not saved in routine examinations.MethodsWe propose a method to generate large amounts of ultrasound images from other modalities and from arbitrary positions, such that this pipeline can later be used by learning algorithms for navigation. We present a novel simulation pipeline which uses segmentations from other modalities, an optimized volumetric data representation and GPU-accelerated Monte Carlo path tracing to generate view-dependent and patient-specific ultrasound images.ResultsWe extensively validate the correctness of our pipeline with a phantom experiment, where structures' sizes, contrast and speckle noise properties are assessed. Furthermore, we demonstrate its usability to train neural networks for navigation in an echocardiography view classification experiment by generating synthetic images from more than 1,000 patients. Networks pre-trained with our simulations achieve significantly superior performance in settings where large real datasets are not available, especially for under-represented classes.DiscussionThe proposed approach allows for fast and accurate patient-specific ultrasound image generation, and its usability for training networks for navigation-related tasks is demonstrated.
Multiparameter ranking of carbazoles for anti-trypanosome lead discovery
Authors: Sharma Amrita , Sanz-Rodriguez Carlos E. , Pollastri Michael P. , Purmal Andrei , Mensa-Wilmot Kojo 
Published: August 2024

The criteria for the progression of hits in the discovery of leads for human African trypanosomiasis (HAT), a neglected disease caused by the microbial eukaryote Trypanosoma brucei, are not standardized. Hits are advanced upon meeting thresholds for drug-like molecules. Following those principles, pharmacokinetics (Cmax and AUC0–6h) and anti-trypanosome characteristics predicted the arrest of T. brucei proliferation in mice by three curaxins. Unexpectedly, while CBL0137 cured HAT in a mouse model, CBL0174 and CBL0187—structural analogs of CBL0137 with similar drug-like properties—failed to control T. brucei division. We here propose an alternative strategy that integrates physicochemical, metabolic, pharmacokinetic, pharmacodynamic, tissue distribution, and trypanocidality parameters into calculating a score for ranking compounds in hit-to-lead campaigns. Data from our studies of curaxins support the feasibility of this goal. Serum dropped the anti-trypanosome potency of CBL0174 and CBL0187 considerably. Delayed trypanocidal concentrations (DTC25 and DTC90) were used to study modes of curaxin actions in trypanosomes. Efficacy of CBL0137 in mice correlated with (i) a high AUC0–6h:DTC90 ratio, (ii) blocking of transferrin endocytosis, and (iii) the inhibition of protein synthesis. Hydroxylation of the carbazole prevented CBL0137 from inhibiting endocytosis of transferrin. The multiparametric score “Curaxin HAT lead efficacy (CHLE)” score was calculated using pharmacokinetic, physicochemical, metabolic, brain exposure, and pharmacodynamic data; CBL0137 was the highest scoring hit. Complementing these observations and predictive of performance of curaxins in mice, CBL0137, but not CBL0174 or CBL0187, was trypanocidal after the exposure of trypanosomes to AUC0–6h amounts of the hits for 6 hours in vitro. We discuss a role for CHLE scores in ranking curaxins for anti-HAT lead discovery. The principles used to develop CHLE scores may be used to calculate new ones for other scaffolds during the discovery of leads for HAT or other infectious diseases.
The causality between use of glucocorticoids and risk of pancreatitis: a Mendelian randomization study
Authors: Lin Wenfeng , Zheng Qiqi , Wang Xiaorong , Lin Xiaolu , Ni Xixi , Pan Jingye , Zippi Maddalena , Fiorino Sirio , Hong Wandong 
Published: August 2024

Background and aimTo date, the association between glucocorticoid use and the risk of pancreatitis remains controversial. The aim of this study was the investigation of this possible relationship.MethodsWe carried out a two-sample Mendelian randomization (MR) analysis using GWAS data from European ancestry, East Asian descendants and the FinnGen Biobank Consortium to evaluate this potential causal relationship. Genetic variants associated with glucocorticoid use were selected based on genome-wide significance (p &lt; 5×10-8).ResultsOur MR analysis of European ancestry data revealed no significant causal relationship between glucocorticoid use and AP (IVW: OR=1.084, 95% CI= 0.945-1.242, P=0.249; MR-Egger: OR=1.049, 95% CI= 0.686-1.603, P=0.828; weighted median: OR=1.026, 95% CI= 0.863-1.219, P=0.775) or CP (IVW: OR=1.027, 95% CI= 0.850-1.240, P=0.785; MR-Egger: OR= 1.625, 95% CI= 0.913-2.890, P= 0.111; weighted median: OR= 1.176, 95% CI= 0.909-1.523, P= 0.218). Sensitivity analyses, including MR-Egger and MR-PRESSO, indicated no evidence of pleiotropy or heterogeneity, confirming the robustness of our findings. Multivariable MR analysis adjusted for alcohol consumption, BMI, cholelithiasis and C-reactive protein levels supported these findings. Replicated analysis was performed on datasets from the FinnGen Biobank Consortium and East Asian descendants, and similar results were obtained.ConclusionsThis MR analysis suggests that there is no causal association between glucocorticoid use and the risk of pancreatitis.
Dysregulated gene expression of SUMO machinery components induces the resistance to anti-PD-1 immunotherapy in lung cancer by upregulating the death of peripheral blood lymphocytes
Authors: Wang Ying , Sun Chao , Liu Mengmeng , Xu Panyang , Li Yanyan , Zhang Yongsheng , Huang Jing 
Published: August 2024

BackgroundThe majority of patients with lung cancer exhibit drug resistance after anti-PD-1 immunotherapy, leading to shortened patient survival time. Previous studies have suggested an association between epigenetic abnormalities such as methylation and clinical response to anti-PD-1 immunotherapy, while the role of SUMOylation in resistance to anti-PD-1 antibody immunotherapy is still unclear.MethodsHere, the mRNA expression of 15 SUMO machinery components in PBMC from lung cancer patients receiving anti-PD-1 immunotherapy were analyzed using real-time PCR. Base on the percentage change in mRNA levels, the relationship between the expression of SUMO machinery components and outcomes of anti-PD-1 immunotherapy, and the influencing factors of SUMOylation were evaluated. PBMC was treated with different concentrations of 2-D08 (a specific inhibitor of SUMOylation) in vitro, and analyzed the activation and the death rates of lymphocyte subsets by flow cytometry analysis.ResultsA predictive method, base on the gene expression of three SUMO machinery components (SUMO1, SUMO3 and UBE2I), were developed to distinguish non-responders to PD-1 inhibitors. Furthermore, the number of lymphocytes in peripheral blood significantly reduced in the dysregulated SUMOylation groups (the percentage change &gt;100 or -50 ~ -100 groups). In vitro studies confirmed that lightly low SUMOylation level improved the activation status of T and NK lymphocytes, but extremely low SUMOylation level lead to the increased death rates of lymphocytes.ConclusionOur findings implied that dysregulated gene expression of SUMO machinery components could induce the resistance of anti-PD-1 immunotherapy in lung cancer by upregulating the death of peripheral blood lymphocytes. These data might provide effective circulating biomarkers for predicting the efficacy of anti-PD-1 immunotherapy, and uncovered a novel regulatory mechanism of resistance to anti-PD-1 immunotherapy.
High socioeconomic impact on prescription behavior despite unrestricted access to disease-modifying therapies in people with multiple sclerosis
Authors: Samadzadeh S. , Havla J. , Lepka K. , Brinks R. , Meuth S. G. , Klotz L. , Albrecht P. 
Published: August 2024

BackgroundEconomic and health care restraints strongly impact on drug prescription for chronic diseases. We aimed to identify potential factors for prescription behavior in chronic disease. Multiple sclerosis was chosen as a model disease due to its chronic character, incidence, and high socioeconomic impact.MethodsGermany was used as a model country as the health-care system is devoid of economic and drug availability restraints. German statutory health insurance data were analyzed retrospectively. The impact of number of university hospitals and neurologists as well as the gross domestic product (GDP) as potential factors on prescriptions of platform and high-efficacy disease-modifying therapies (DMTs) was analyzed.ResultsPrescription of platform DMTs increased over time in almost all federal states with varying degree of increase. Univariate regression analysis showed that the prescription volume of platform DMTs positively correlated with the number of university hospitals and neurologists, as well as the GDP per federal state. Stepwise forward regression analysis including all potential factors indicated a statistically significant model for platform DMT (R2 = 0.55; 95%-CI [0.28, 0.82]; p=0.001) revealing GDP as the main contributor. This was confirmed in the independent analysis.ConclusionThis study illustrates that even without overt drug prescription inequity, access to medication is not evenly distributed and depends on economic strength and regional medical care density.
A natural vertical distribution calculation scheme for salinity simulation in free-surface model with quasi-stationary coordinates
Authors: Li Yundong , Han Guijun , Li Wei , Wu Xiaobo , Cao Lige , Zhou Gongfu 
Published: August 2024

IntroductionSalinity is a key variable in the dynamic and thermal balance of the entire climate system. To address the complexities of diverse terrains and fluctuating ocean waves, we commonly use free-surface models with quasi-stationary (e.g. height, pressure, or terrain following) coordinates for simulating salinity. In such models, the vertical grid dynamically adjusts with the undulation of seawater. However, this adjustment also occurs when freshwater enters or exits the ocean. Freshwater-induced salinity changes at the ocean’s surface are artificially distributed to each vertical layer within a model time step. This means that the freshwater at the ocean surface instantaneously and directly affects the seafloor. This process is different from physical diffusion processes. The diffusion effects caused by the influx and outflow of freshwater have a very small impact on the seafloor. This error leads to salinity non-conservation and disrupts the vertical distribution structure of salinity. Previous studies have also addressed this issue with solutions such as the vertical Lagrangian-remap method.MethodThis paper proposes a natural vertical distribution calculation scheme (NVDCS) which is different from the approaches of our predecessors. In the discrete formulation of the original ocean equations, freshwater flux is introduced to ensure salinity conservation. In each model time step, by calculating the seawater volume changes due to freshwater inflow or outflow, as well as the vertical grid changes caused by sea surface undulations, the aforementioned artificial error is eliminated from each vertical layer.DiscussionThis scheme ensures that changes in the vertical coordinates of each layer result solely from internal oceanic dynamic processes, avoiding the instantaneous and directly impact of surface freshwater. Ultimately, the influence of freshwater is confined to the ocean surface.ResultsThis method is straightforward to implement and user-friendly. Sensitivity experiments indicate that in free-surface models, quasi-stationary coordinates introduce artificial errors. The proposed calculation scheme not only eliminates this error but also achieves a better vertical distribution structure than using virtual salt flux, while ensuring salinity conservation.
Machine learning-based risk prediction of acute kidney disease and hospital mortality in older patients
Authors: Wang Xinyuan , Xu Lingyu , Guan Chen , Xu Daojun , Che Lin , Wang Yanfei , Man Xiaofei , Li Chenyu , Xu Yan 
Published: August 2024

IntroductionAcute kidney injury (AKI) is a prevalent complication in older people, elevating the risks of acute kidney disease (AKD) and mortality. AKD reflects the adverse events developing after AKI. We aimed to develop and validate machine learning models for predicting the occurrence of AKD, AKI and mortality in older patients.MethodsWe retrospectively reviewed the medical records of older patients (aged 65 years and above). To explore the trajectory of kidney dysfunction, patients were categorized into four groups: no kidney disease, AKI recovery, AKD without AKI, or AKD with AKI. We developed eight machine learning models to predict AKD, AKI, and mortality. The best-performing model was identified based on the area under the receiver operating characteristic curve (AUC) and interpreted using the Shapley additive explanations (SHAP) method.ResultsA total of 22,005 patients were finally included in our study. Among them, 4,434 patients (20.15%) developed AKD, 4,000 (18.18%) occurred AKI, and 866 (3.94%) patients deceased. Light gradient boosting machine (LGBM) outperformed in predicting AKD, AKI, and mortality, and the final lite models with 15 features had AUC values of 0.760, 0.767, and 0.927, respectively. The SHAP method revealed that AKI stage, albumin, lactate dehydrogenase, aspirin and coronary heart disease were the top 5 predictors of AKD. An online prediction website for AKD and mortality was developed based on the final models.DiscussionThe LGBM models provide a valuable tool for early prediction of AKD, AKI, and mortality in older patients, facilitating timely interventions. This study highlights the potential of machine learning in improving older adult care, with the developed online tool offering practical utility for healthcare professionals. Further research should aim at external validation and integration of these models into clinical practice.
A retrospective study of ophthalmologic presentation, management, and outcomes in pediatric patients admitted with abusive head trauma
Authors: Yin Jiawei , Peng Jie , Zhang Xuerui , Yang Yuan , Gu Victoria Y. , Zhang Wenting , Liu Huanyu , Xiao Haodong , Xu Yu , Zhao Peiquan 
Published: August 2024

BackgroundAbusive head trauma (AHT) is a severe form of physical abuse leading to significant morbidity and mortality in children, often presenting with complex brain injuries. Among the varied manifestations, ophthalmologic presentations are critical yet underexplored, which may provide essential clues for early diagnosis and management, improving long-term visual and neurological outcomes.ObjectiveThis study aims to explore the manifestation, management, and outcomes of AHT cases within a single center in China over a five-year period, with a focus on the importance of ophthalmologic evaluation in enhancing the diagnosis, management, and outcome predictions of AHT.MethodsA retrospective case series was conducted at a single institution, involving infants diagnosed with AHT from 2019 to 2023. Data on demographics, medical histories, and clinical management were collected. Ophthalmologic examinations including fundus photography, ocular B-scan ultrasound and fundus fluorescein angiography (FFA), were performed to evaluate retinal vasculature and identify peripheral ischemic retina (PIR). Statistical analyses were performed using SPSS ver. 26.0.ResultsEight AHT patients (16 eyes) were included in the study. Bilateral ocular involvement was observed in all patients, with 81.25% exhibiting retinal hemorrhages (RH). Other manifestations included retinal detachment (31.25%) and optic nerve atrophy (18.75%). Clinical interventions varied, with 68.75% of patients undergoing treatments such as laser photocoagulation and anti-vascular endothelial growth factor (VEGF) injections. Among all eyes, 75% showed resolution of RH. Despite treatment, some patients progressed to severe conditions such as retinal detachment (RD) and iris neovascularization (INV).ConclusionThis study emphasizes the importance of a multidisciplinary approach in the diagnosis and management of AHT, particularly by integrating ophthalmological perspectives into patient care. These findings contribute to the understanding of ophthalmologic presentations in AHT.
Mechanism of action of quercetin in regulating cellular autophagy in multiple organs of Goto-Kakizaki rats through the PI3K/Akt/mTOR pathway
Authors: Guo Zhiqun , Zhang Jingyu , Li Mianxin , Xing Zengwei , Li Xi , Qing Jiaqi , Zhang Yuan , Zhu Lemei , Qi Mingxu , Zou Xuemin 
Published: August 2024

ObjectiveThis experimental study investigated the protective function of quercetin on the liver, spleen, and kidneys of Goto-Kakizaki (GK) rats and explores its mechanism of action on autophagy-related factors and pathways.Materials and methodsGK rats were randomly divided into three groups: DM, DM + L-Que, and DM + H-Que, with age-matched Wistar rats serving as the control group. The control and DM groups were gavaged with saline, and the quercetin-treated group was gavaged with quercetin for 8 weeks each. Weekly blood glucose levels were monitored. Upon conclusion of the experiment, blood samples were gathered for lipid and hepatic and renal function analyses. The histopathologic morphology and lipid deposition in rats were examined. Disease-related targets were identified using molecular docking methods and network pharmacology analysis. Subsequently, immunohistochemical analysis was performed, followed by Western blotting to evaluate the levels of autophagy-related proteins and proteins in the AKT/PI3K/mTOR pathway, as well as their phosphorylation levels.ResultsThe results showed that, compared with the control group, the DM group exhibited significant increases in blood glucose, serum liver and kidney markers, liver fat vacuoles, and inflammatory cell infiltration. Immunohistochemistry (IHC) results indicated that quercetin reduced the extensive expression of AKT, P62, and mTOR in the liver and spleen of diabetic rats. The expression of autophagy and pathway-related proteins, such as P62, PI3K, P-PI3K, Akt, P-AKT, mTOR, and P-mTOR, was upregulated, while the expression of LC3A/LC3B, Beclin-1, Pink-1, and Parkin was downregulated. Conversely, the quercetin group showed a reduction in liver and kidney injury serum markers by decreasing lipid deposition and cell necrosis, indicating that quercetin has protective effects on the liver, spleen, and kidneys of GK rats. Additionally, in the quercetin group, the expression of autophagy and pathway-related proteins such as LC3A/LC3B, Beclin-1, Pink-1, and Parkin was upregulated, while the expression of P62, PI3K, P-PI3K, Akt, P-AKT, mTOR, and P-mTOR was downregulated, with statistically significant correlations.ConclusionQuercetin markedly ameliorates liver, spleen, and kidney damage in GK rats, potentially through the inhibition of the PI3K/Akt/mTOR pathway, promoting autophagy. This research offers a rationale to the therapeutic potential of quercetin in mitigating organ damage associated with diabetes.
Global, regional, and national burden of syphilis, 1990–2021 and predictions by Bayesian age-period-cohort analysis: a systematic analysis for the global burden of disease study 2021
Authors: Yu Wenxia , You Xiaoyan , Luo Wei 
Published: August 2024

ObjectiveTo comprehensively assess the global burden of syphilis and related risk factors over 1990–2021, forecast future disease trends, and understand the impact of syphilis on global health.MethodsGlobal Burden of Disease Study 2021 (GBD 2021) data were used for age-, sex-, and region-stratified analysis of the numbers and age-standardized rates (per 100,000 population) of syphilis incidence, prevalence, deaths, and disability-adjusted life years (DALYs). Next, a differential analysis of syphilis risk factors was performed. Finally, trends for years after 2021 were predicted using Bayesian age–period–cohort (BAPC) prediction models.ResultsIn 2021, the total number of syphilis prevalence globally was 70,541,482.80 (95% uncertainty interval: 54,910,897.66–88,207,651.97), with the highest numbers noted in Central Sub-Saharan Africa [4,622.60 (95% uncertainty interval: 3,591.97–5,753.45)]. Over 1990–2021, the global age-standardized prevalence and incidence rates increased, whereas the age-standardized death and DALY rates decreased. Among all groups, infants aged &lt;5 years demonstrated the highest age-standardized DALY rates. Moreover, the lower the sociodemographic index (SDI), the higher was the age-standardized rate. The primary factor contributing to syphilis disease burden was identified to be unsafe sex. BAPC analysis revealed an overall increase in age-standardized prevalence rate in the &lt;5-year age group over 1990–2035, and the highest age-standardized prevalence rate occurred in the 25–34-year age group.ConclusionBetween 1990 and 2021, syphilis occurrence and prevalence increased consistently. Projections indicated a continual increase in syphilis incidence in children aged &lt;5 years, and age-standardized prevalence rates were the highest in adults aged 25–34 years. Our results regarding the epidemiological trends of syphilis and its variations across regions, age groups, and sexes may aid policymakers in addressing the global impact of the disease effectively.