bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Introduction

Acute 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.

Methods

We 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.

Results

A 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.

Discussion

The 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

Background

Abusive 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.

Objective

This 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.

Methods

A 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.

Results

Eight 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).

Conclusion

This 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.
Current perspectives in the management of sepsis and septic shock
Authors: Chiscano-Camón Luis , Ruiz-Sanmartin Adolf , Bajaña Ivan , Bastidas Juliana , Lopez-Martinez Rocio , Franco-Jarava Clara , Gonzalez Juan José , Larrosa Nieves , Riera Jordi , Nuvials-Casals Xavier , Ruiz-Rodríguez Juan Carlos , Ferrer Ricard
Published: August 2024

Within patients with sepsis, there exists significant heterogeneity, and while all patients should receive conventional therapy, there are subgroups of patients who may benefit from specific therapies, often referred to as rescue therapies. Therefore, the identification of these specific patient subgroups is crucial and lays the groundwork for the application of precision medicine based on the development of targeted interventions. Over the years, efforts have been made to categorize sepsis into different subtypes based on clinical characteristics, biomarkers, or underlying mechanisms. For example, sepsis can be stratified into different phenotypes based on the predominant dysregulated host response. These phenotypes can range from hyperinflammatory states to immunosuppressive states and even mixed phenotypes. Each phenotype may require different therapeutic approaches to improve patient outcomes. Rescue strategies for septic shock may encompass various interventions, such as immunomodulatory therapies, extracorporeal support (e.g., ECMO), or therapies targeted at specific molecular or cellular pathways involved in the pathophysiology of sepsis. In recent years, there has been growing interest in precision medicine approaches to sepsis and phenotype identification. Precision medicine aims to tailor treatments to each individual patient based on their unique characteristics and disease mechanisms.
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

Objective

This 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 methods

GK 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.

Results

The 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.

Conclusion

Quercetin 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

Objective

To 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.

Methods

Global 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.

Results

In 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 <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 <5-year age group over 1990–2035, and the highest age-standardized prevalence rate occurred in the 25–34-year age group.

Conclusion

Between 1990 and 2021, syphilis occurrence and prevalence increased consistently. Projections indicated a continual increase in syphilis incidence in children aged <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.
Caspofungin enhances the potency of rifampin against Gram-negative bacteria
Authors: Li Haotian , Zhu Xiaojing , Zhang Xing , Dong Changjiang
Published: August 2024

Introduction

Developing antibiotic adjuvants is an effective strategy to combat antimicrobial resistance (AMR). The envelope of Gram-negative bacteria (GNB) is a barrier to prevent the entry of antibiotics, making it an attractive target for novel antibiotic and adjuvant development.

Methods and Results

In this study, we identified Caspofungin acetate (CAS) as an antibiotic adjuvant against GNB in the repurposing screen of 3,158 FDA-approved drugs. Checkerboard assays suggested that CAS could enhance the antimicrobial activity of rifampin or colistin against various GNB strains in vitro, Moreover, Galleria mellonella larvae infection model also indicated that CAS significantly potentiated the efficacy of rifampin against multidrug-resistant Escherichia coli 72 strain in vivo. Most importantly, resistance development assay showed that CAS was less susceptible to accelerating the resistance development of drug-sensitive strain E. coli MG1655. Functional studies and RNA-seq analysis confirmed that the mechanisms by which CAS enhanced the antimicrobial activities of antibiotics were involved in permeabilizing the bacterial cell envelope, disrupting proton motive force and inhibiting bacterial biofilm formation. Additionally, it has been found that PgaC is the CAS target and enzymatic assay has confirmed the inhibition activity.

Discussion

Our results illustrate the feasibility of CAS as an antibiotic adjuvant against GNB, which is an alternative strategy of anti-infection.
FGF21 upregulation by hepatitis C virus via the eIF2α-ATF4 pathway: implications for interferon signaling suppression and TRIM31-mediated TSC degradation
Authors: Liu Liang , Ito Masahiko , Sakai Satoshi , Liu Jie , Ohta Kazuyoshi , Saito Kenji , Nakashima Kenji , Satoh Shinya , Konno Alu , Suzuki Tetsuro
Published: August 2024

Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases and is known to induce endoplasmic reticulum (ER) stress, which alters cellular homeostasis and metabolic processes. While ER stress is implicated in HCV-related diseases, its precise role remains unclear. This study identifies fibroblast growth factor 21 (FGF21) as a key host factor significantly upregulated by HCV infection. Mechanistic analyses reveal that the activation of the FGF21 promoter by HCV is primarily mediated by the transcription factor ATF4, which is upregulated through the phosphorylation of eIF2α induced by ER stress. Additionally, CREBH activation further enhances ATF4 expression, contributing to increased FGF21 levels. TRIB3, upregulated by ATF4, acts as a negative regulator of FGF21 expression. The study also identifies FGF21-dependent upregulation of SOCS2 and TRIM31 in HCV-infected cells. SOCS2 contributes to the suppression of type 1 interferon signaling, aiding viral persistence, while TRIM31 promotes the degradation of the tumor suppressor protein TSC, activating the mTORC1 pathway and potentially promoting liver cell proliferation. These findings suggest that FGF21 upregulation in HCV-infected cells may play a role in both immune response regulation and cell proliferation, contributing to sustained viral infection and disease progression.
Stroke rehabilitation: from diagnosis to therapy
Authors: Li Xiaohong , He Yanjin , Wang Dawu , Rezaei Mohammad J.
Published: August 2024

Stroke remains a significant global health burden, necessitating comprehensive and innovative approaches in rehabilitation to optimize recovery outcomes. This paper provides a thorough exploration of rehabilitation strategies in stroke management, focusing on diagnostic methods, acute management, and diverse modalities encompassing physical, occupational, speech, and cognitive therapies. Emphasizing the importance of early identification of rehabilitation needs and leveraging technological advancements, including neurostimulation techniques and assistive technologies, this manuscript highlights the challenges and opportunities in stroke rehabilitation. Additionally, it discusses future directions, such as personalized rehabilitation approaches, neuroplasticity concepts, and advancements in assistive technologies, which hold promise in reshaping the landscape of stroke rehabilitation. By delineating these multifaceted aspects, this manuscript aims to provide insights and directions for optimizing stroke rehabilitation practices and enhancing the quality of life for stroke survivors.
Management of Meige syndrome with bilateral trigeminal and facial nerves combing
Authors: Ying Tingting , Wang Haopeng , Tang Yinda , Zhao Hua , Cai Xiaomin , Shen Yiman , Wang Baimiao , Zhu Wanchun , Zhou Ping , Zhang Xin , Zhong Jun , Wang Xinjun , Fu Xudong , Zhu Jin , Zhang Weituo , Li Shiting
Published: August 2024

Objective

Meige syndrome (MS) is an adult-onset segmental dystonia for which no satisfactory remedy currently exists. Our team developed a novel surgical approach called bilateral trigeminal/facial nerve combing (BTFC). This study aimed to evaluate the outcomes of patients who underwent BFTC (Clinical Trial Registry Number: ChiCTR2000033481).

Method

We assigned 22 patients with MS to undergo BTFC. The primary outcome was assessed using the movement subscale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-M) at 12 months postoperatively. The second outcome was evaluated using the Medical Outcome Study (MOS) 36-item Short Form Health Survey (SF-36), the dysfunction subscale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-D), and the sub-item scores of the BFMDRS-M. Safety outcomes included the House-Brackmann (HB) functional grading score and the visual analog scale (VAS) for facial numbness.

Results

At the final follow-up at 12 months, the BFMDRS-M showed a mean improvement of 70.7% from baseline. Mean scores of the BFMDRS-M sub-motor (including the eyes, mouth, and speech/swallowing) improved by 65.6, 81.00, and 60%, respectively. The median score of the total BFMDRS-D score was 0.70 ± 1.17 compared with 1.86 ± 2.21 at baseline. There were no serious operative complications in this population. The quality of life of the patients significantly improved (P < 0.05).

Conclusion

BFTC has proven to be effective in relieving the symptoms of Meige syndrome. This novel surgical approach offers a new alternative treatment for patients who have failed to respond to medications, botulinum toxin injections, and deep brain stimulation (DBS).

Clinical Trial Registration

https://www.chictr.org.cn/bin/project/edit?pid=54567, ChiCTR2000033481.
Dominating Alzheimer's disease diagnosis with deep learning on sMRI and DTI-MD
Authors: Li Yuxia , Chen Guanqun , Wang Guoxin , Zhou Zhiyi , An Shan , Dai Shipeng , Jin Yuxin , Zhang Chao , Zhang Mingkai , Yu Feng
Published: August 2024

Background

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder that has become one of the major health concerns for the elderly. Computer-aided AD diagnosis can assist doctors in quickly and accurately determining patients' severity and affected regions.

Methods

In this paper, we propose a method called MADNet for computer-aided AD diagnosis using multimodal datasets. The method selects ResNet-10 as the backbone network, with dual-branch parallel extraction of discriminative features for AD classification. It incorporates long-range dependencies modeling using attention scores in the decision-making layer and fuses the features based on their importance across modalities. To validate the effectiveness of our proposed multimodal classification method, we construct a multimodal dataset based on the publicly available ADNI dataset and a collected XWNI dataset, which includes examples of AD, Mild Cognitive Impairment (MCI), and Cognitively Normal (CN).

Results

On this dataset, we conduct binary classification experiments of AD vs. CN and MCI vs. CN, and demonstrate that our proposed method outperforms other traditional single-modal deep learning models. Furthermore, this conclusion also confirms the necessity of using multimodal sMRI and DTI data for computer-aided AD diagnosis, as these two modalities complement and convey information to each other. We visualize the feature maps extracted by MADNet using Grad-CAM, generating heatmaps that guide doctors' attention to important regions in patients' sMRI, which play a crucial role in the development of AD, establishing trust between human experts and machine learning models.

Conclusion

We propose a simple yet effective multimodal deep convolutional neural network model MADNet that outperforms traditional deep learning methods that use a single-modality dataset for AD diagnosis.
Phytochemical profiling and evaluation of antimicrobial activities of common culinary spices: Syzygium aromaticum (clove) and Piper nigrum (black pepper)
Authors: Zhao Kexin , Wonta Kou B. , Xia Jinquan , Zhong Fuhua , Sharma Vipasha
Published: August 2024

Background

The increasing resistance of microbial pathogens to conventional antibiotics necessitates the exploration of alternative antimicrobial agents. This study aims to evaluate the antimicrobial potential and phytochemical properties of Syzygium aromaticum (clove) and Piper nigrum (black pepper) extracts, both of which are known for their historical use in traditional medicine and culinary applications.

Methods

Hydroalcoholic and aqueous extracts of clove and black pepper were prepared. The antimicrobial activity of these extracts was assessed using the disk diffusion method against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger. Minimum inhibitory concentration (MIC) was determined using the broth dilution method. Qualitative phytochemical screening identified the presence of key bioactive compounds, while quantitative analysis measured total phenolic and flavonoid contents. LC-HRMS/MS analysis of ethanolic extracts was performed.

Results

Both spices extracts exhibited significant antimicrobial activity, with inhibition zones ranging from 14 to 18 mm. clove showed superior antimicrobial efficacy compared to black paper, particularly against fungi. MIC values ranged between 3 mg/mL and 6 mg/mL for both spices. Phytochemical analysis revealed higher total phenolic and flavonoid contents in clove, with hydroalcoholic extracts showing greater concentrations than aqueous extracts. HPLC quantified higher eugenol content in clove extracts and higher piperine content in black pepper extracts. The differences in bioactive compound content were statistically significant (p < 0.05).

Conclusion

The study confirms that both spices possess significant antimicrobial properties, attributable to their rich phytochemical composition, particularly phenolics and flavonoids. Clove exhibited slightly superior antimicrobial activity compared to black paper. These findings support the potential use of these spices as complementary antimicrobial agents. Further research should investigate their synergistic effects with conventional antibiotics and explore their applications in food preservation and alternative medicine.
Single versus multiple fraction stereotactic radiosurgery for medium-sized brain metastases (4-14 cc in volume): reducing or fractionating the radiosurgery dose?
Authors: Reinhardt Philipp , Ahmadli Uzeyir , Uysal Emre , Shrestha Binaya Kumar , Schucht Philippe , Hakim Arsany , Ermiş Ekin
Published: August 2024

Background and purpose

Stereotactic radiosurgery (SRS) of brain metastases (BM) and resection cavities is a widely used and effective treatment modality. Based on target lesion size and anatomical location, single fraction SRS (SF-SRS) or multiple fraction SRS (MF-SRS) are applied. Current clinical recommendations conditionally recommend either reduced dose SF-SRS or MF-SRS for medium-sized BM (2–2.9 cm in diameter). Despite excellent local control rates, SRS carries the risk of radionecrosis (RN). The purpose of this study was to assess the 12-months local control (LC) rate and 12-months RN rate of this specific patient population.

Materials and methods

This single-center retrospective study included 54 patients with medium-sized intact BM (n=28) or resection cavities (n=30) treated with either SF-SRS or MF-SRS. Follow-up MRI was used to determine LC and RN using a modification of the “Brain Tumor Reporting and Data System” (BT-RADS) scoring system.

Results

The 12-month LC rate following treatment of intact BM was 66.7% for SF-SRS and 60.0% for MF-SRS (p=1.000). For resection cavities, the 12-month LC rate was 92.9%% after SF-SRS and 46.2% after MF-SRS (p=0.013). For intact BM, RN rate was 17.6% for SF-SRS and 20.0% for MF-SRS (p=1.000). For resection cavities, RN rate was 28.6% for SF-SRS and 20.0% for MF-SRS (p=1.000).

Conclusion

Patients with intact BM showed no statistically significant differences in 12-months LC and RN rate following SF-SRS or MF-SRS. In patients with resection cavities the 12-months LC rate was significantly better following SF-SRS, with no increase in the RNFS.
Pilot study: radiomic analysis for predicting treatment response to whole-brain radiotherapy combined temozolomide in lung cancer brain metastases
Authors: Sun Yichu , Liang Fei , Yang Jing , Liu Yong , Shen Ziqiang , Zhou Chong , Xia Youyou
Published: August 2024

Objective

The objective of this study is to assess the viability of utilizing radiomics for predicting the treatment response of lung cancer brain metastases (LCBM) to whole-brain radiotherapy (WBRT) combined with temozolomide (TMZ).

Methods

Fifty-three patients diagnosed with LCBM and undergoing WBRT combined with TMZ were enrolled. Patients were divided into responsive and non-responsive groups based on the RANO-BM criteria. Radiomic features were extracted from contrast-enhanced the whole brain tissue CT images. Feature selection was performed using t-tests, Pearson correlation coefficients, and Least Absolute Shrinkage And Selection (LASSO) regression. Logistic regression was employed to construct the radiomics model, which was then integrated with clinical data to develop the nomogram model. Model performance was evaluated using receiver operating characteristic (ROC) curves, and clinical utility was assessed using decision curve analysis (DCA).

Results

A total of 1834 radiomic features were extracted from each patient's images, and 3 features with predictive value were selected. Both the radiomics and nomogram models exhibited satisfactory predictive performance and clinical utility, with the nomogram model demonstrating superior predictive value. The ROC analysis revealed that the AUC of the radiomics model in the training and testing sets were 0.776 and 0.767, respectively, while the AUC of the nomogram model were 0.799 and 0.833, respectively. DCA curves demonstrated that both models provided benefits to patients across various thresholds.

Conclusion

Radiomic-defined image biomarkers can effectively predict the treatment response of WBRT combined with TMZ in patients with LCBM, offering potential to optimize treatment decisions for this condition.
Hematological indicator-based machine learning models for preoperative prediction of lymph node metastasis in cervical cancer
Authors: Zhao Huan , Wang Yuling , Sun Yilin , Wang Yongqiang , Shi Bo , Liu Jian , Zhang Sai
Published: August 2024

Background

Lymph node metastasis (LNM) is an important prognostic factor for cervical cancer (CC) and determines the treatment strategy. Hematological indicators have been reported as being useful biomarkers for the prognosis of a variety of cancers. This study aimed to evaluate the feasibility of machine learning models characterized by preoperative hematological indicators to predict the LNM status of CC patients before surgery.

Methods

The clinical data of 236 patients with pathologically confirmed CC were retrospectively analyzed at the Gynecology Oncology Department of the First Affiliated Hospital of Bengbu Medical University from November 2020 to August 2022. The least absolute shrinkage and selection operator (LASSO) was used to select 21 features from 35 hematological indicators and for the construction of 6 machine learning predictive models, including Adaptive Boosting (AdaBoost), Gaussian Naive Bayes (GNB), and Logistic Regression (LR), as well as Random Forest (RF), Support Vector Machines (SVM), and Extreme Gradient Boosting (XGBoost). Evaluation metrics of predictive models included the area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, and F1-score.

Results

RF has the best overall predictive performance for ten-fold cross-validation in the training set. The specific performance indicators of RF were AUC (0.910, 95% confidence interval [CI]: 0.820–1.000), accuracy (0.831, 95% CI: 0.702–0.960), specificity (0.835, 95% CI: 0.708–0.962), sensitivity (0.831, 95% CI: 0.702–0.960), and F1-score (0.829, 95% CI: 0.696–0.962). RF had the highest AUC in the testing set (AUC = 0.854).

Conclusion

RF based on preoperative hematological indicators that are easily available in clinical practice showed superior performance in the preoperative prediction of CC LNM. However, investigations on larger external cohorts of patients are required for further validation of our findings.
Assessment of pathological grade and variants of bladder cancer with a continuous-time random-walk diffusion model
Authors: Wang Wei , Wu Jingyun , Shen Qi , Li Wei , Xue Ke , Yang Yuxin , Qiu Jianxing
Published: August 2024

Purpose

To evaluate the efficacy of high b-value diffusion-weighted imaging (DWI) with a continuous-time random-walk (CTRW) diffusion model in determining the pathological grade and variant histology (VH) of bladder cancer (BCa).

Methods

A total of 81 patients (median age, 70 years; range, 35-92 years; 18 females; 66 high grades; 30 with VH) with pathologically confirmed bladder urothelial carcinoma were retrospectively enrolled and underwent bladder MRI on a 3.0T MRI scanner. Multi-b-value DWI was performed using 11 b-values. Three CTRW model parameters were obtained: an anomalous diffusion coefficient (D) and two parameters reflecting temporal (α) and spatial (β) diffusion heterogeneity. The apparent diffusion coefficient (ADC) was calculated using b0 and b800. D, α, β, and ADC were statistically compared between high- and low-grade BCa, and between pure urothelial cancer (pUC) and VH. Comparisons were made using the Mann–Whitney U test between different pathological states. Receiver operating characteristic curve analysis was used to assess performance in differentiating the pathological states of BCa.

Results

ADC, D, and α were significantly lower in high-grade BCa compared to low-grade, and in VH compared to pUC (p < 0.001), while β showed no significant differences (p > 0.05). The combination of D and α yielded the best performance for determining BCa grade and VH (area under the curves = 0.913, 0.811), significantly outperforming ADC (area under the curves = 0.823, 0.761).

Conclusion

The CTRW model effectively discriminated pathological grades and variants in BCa, highlighting its potential as a noninvasive diagnostic tool.
Clinical insights into nanomedicine and biosafety: advanced therapeutic approaches for common urological cancers
Authors: Fattahi Mohammad Reza , Dehghani Mansoureh , Paknahad Somayyeh , Rahiminia Shafa , Zareie Deniz , Hoseini Behzad , Oroomi Tahmineh Rajaee , Motedayyen Hossein , Arefnezhad Reza
Published: August 2024

Urological cancers including those of the prostate, bladder, and kidney, are prevalent and often lethal malignancies besides other less common ones like testicular and penile cancers. Current treatments have major limitations like side effects, recurrence, resistance, high costs, and poor quality of life. Nanotechnology offers promising solutions through enhanced diagnostic accuracy, targeted drug delivery, controlled release, and multimodal imaging. This review reflects clinical challenges and nanomedical advances across major urological cancers. In prostate cancer, nanoparticles improve delineation and radiosensitization in radiation therapy, enable fluorescent guidance in surgery, and enhance chemotherapy penetration in metastatic disease. Nanoparticles also overcome bladder permeability barriers to increase the residence time of intravesical therapy and chemotherapy agents. In renal cancer, nanocarriers potentiate tyrosine kinase inhibitors and immunotherapy while gene vectors and zinc oxide nanoparticles demonstrate antiproliferative effects. Across modalities, urological applications of nanomedicine include polymeric, liposomal, and metal nanoparticles for targeted therapy, prodrug delivery, photodynamic therapy, and thermal ablation. Biosafety assessments reveal favorable profiles but clinical translation remains limited, necessitating further trials. In conclusion, nanotechnology holds significant potential for earlier detection, precise intervention, and tailored treatment of urological malignancies, warranting expanded research to transform patient outcomes.
Clinacanthus nutans extract lowers periodontal inflammation under high-glucose conditions via inhibiting NF-κB signaling pathway
Authors: Thongyim Saruda , Wright Thomas A. , Sattayawat Pachara , Kaewkod Thida , Baillie George S. , Tragoolpua Yingmanee , Jangsutthivorawat Siriphorn , Panya Aussara
Published: August 2024

Periodontal disease is more prevalent in patients with diabetes, and it has a negative impact on their quality of life. Inhibiting the infection and inflammation processes that cause periodontal disease can reduce the severity of the disease and chances of serious complications. In this study, we aimed to demonstrate the effectiveness of Clinacanthus nutans extract in reducing the inflammation in gingival fibroblast cells induced by Porphyromonas gingivalis lipopolysaccharide (LPS). Stimulation with LPS under high-glucose conditions led to increased inflammation compared to low-glucose conditions. Treatment of C. nutans extract significantly reduced the expression of these pro-inflammatory cytokines and chemokines. At a concentration of 50 μg/mL, it reduced the relative expression of IL6, IL8, and CXCL10 to 0.51 ± 0.09, 0.6 ± 0.19, and 0.09 ± 0.02, respectively, compared to the non-treatment control, accompanied by a decrease in secreted protein as measured by ELISA. Additionally, application of C. nutans extract markedly suppressed the NF-κB signaling pathway by reducing the phosphorylated form of IκBα, NF-κB p65, and nuclear translocation of NF-κB, along with a decrease in COX2, a key mediator in the inflammatory pathway. Furthermore, analysis of RNA sequencing data indicated that the extract clearly reversed the gene expression changes induced by LPS. This was particularly true for the signaling mediators and inflammatory genes in response to NF-κB, JAK/STAT, and TNF signaling pathways. Our finding highlights the potential of C. nutans extract to alleviate inflammation and suggests its potential as a treatment for periodontal disease in patients with diabetes.
Effects of perioperative steroid use on surgical stress and prognosis in patients undergoing hepatectomy: a systematic review and meta-analysis of randomized controlled trials
Authors: Zhong Furui , Yang Hua , Peng Xuefeng , Zeng Kerui
Published: August 2024

The objective of this study was to evaluate the clinical effects of perioperative steroid hormone usage in hepatectomy patients through a comprehensive systematic review and meta-analysis. Prospective randomized controlled trials (RCTs) investigating the perioperative use of steroid hormones in hepatectomy patients were systematically searched using various databases, including PubMed, Medline, Embase, the Cochrane Library, the Chinese Biomedical Literature Database, Wanfang Data, and the CNKI database. Two researchers independently screened and extracted data from selected studies. Data analysis was performed using RevMan 5.3 software. The results revealed significantly lower levels of total bilirubin (standard mean difference [SMD] = −0.7; 95% CI: −1.23 to −0.18; and p = 0.009), interleukin-6 (SMD = −1.02; 95% CI: −1.27 to −0.77; and p < 0.001), and C-reactive protein (SMD = −0 .65; 95% CI: −1 .18 to −0.11; and p = 0.02) on postoperative day 1 (POD 1), as well as a reduced incidence of postoperative complications in the steroid group compared to the placebo group. No significant differences were observed between the two groups regarding alanine aminotransferase (ALT) levels, aspartic aminotransferase (AST) levels, or specific complications such as intra-abdominal infection (p = 0.72), wound infection (p = 0.1), pleural effusion (p = 0.43), bile leakage (p = 0.66), and liver failure (p = 0.16). The meta-analysis results indicate that perioperative steroid usage can effectively alleviate liver function impairment and inflammation response following hepatectomy while improving patient prognosis.
Pomegranate flower polysaccharide improves mastitis in mice by regulating intestinal flora and restoring the blood-milk barrier
Authors: Li Jianlong , Yin Wen , Liang Yuan , Yang Zhaoran , Li Liangliang , Mai Zhanhai , Yu Xingjian , Lu Yabin , Zhang Zhenping , Abula Saifuding , Wu Yi , Wusiman Adelijiang , Guo Qingyong
Published: August 2024

This study explored the inhibitory effect of pomegranate flower polysaccharide (PFPS) on mastitis through in vitro and in vivo models. PFPS is a new type of polysaccharide isolated and extracted from pomegranate flowers. The result revealed that PFPS consists of GalA, Ara, and Gal, and the residues consist of 1,4-GalpA, 1,4-Galp, and 1,3,6-Galp, which contain HG-type and RG-I-type pectin structural domains. In vitro studies showed that PFPS could inhibit LPS-enhanced phagocytosis of RAW 264.7 cells and the release of IL-1β, IL-10, and TNF-α. In vivo, studies showed that PFPS improved xylene-induced mouse ear swelling and carrageenan-induced mouse paw edema by inhibiting inflammatory factors. In the mouse mastitis model, PFPS significantly improved LPS-induced inflammation and oxidative stress in mammary tissue. Intestinal flora sequencing results showed that PFPS could effectively regulate the intestinal flora of mice, reduce the relative abundance of pathogenic bacteria Oscillospira and AF12, and increase the probiotics Blautia, Parabacteroides, Allobaculum, and Clostridiaceae_Clostridium. Therefore, PFPS ultimately played a role in preventing mastitis by regulating the intestinal flora and further improving the blood-milk barrier. This study provides a scientific basis for PFPS as a potential candidate drug for the treatment of mastitis.
Comprehensive fecal metabolomics and gut microbiota study of the protective mechanism of herbal pair Polygonum hydropiper-Coptis chinensis in rats with stress-induced gastric mucosal damage
Authors: Ren Shouzhong , Ren Chenhui , Zhao Yamei , Niu Haiyan , Xie Yiqiang
Published: August 2024

Introduction: Stress-related gastric mucosal lesions (SGMLs) are the most common complication in critical care patients. Previous studies have demonstrated that herbal pair (HP), Polygonum hydropiper-Coptis chinensis (HP P-C) has the anti-SGML effect. However, the underlying mechanism of HP P-C against SGML remains elusive. This study aimed to elucidate how HP P-C extracts exert their protective effects on SGML by examining the role of gut microbiota and metabolites.

Methods: SD rats were pretreated with different doses of HP P-C extracts for 6 days, followed by inducing SGML with water-immersion restraint stress (WIRS). After a comprehensive evaluation of serum and gastric tissue indicators in rats, 16S rRNA sequencing and metabolomics analyses were conducted to assess the impact of HP P-C on the fecal microorganisms and metabolites and their correlation.

Results: Animal experiment suggested that pretreatment with HP P-C effectively reduced the gastric mucosal lesions, remarkably increased superoxide dismutase (SOD) activity in SGML model rats induced by WIRS. 16S rRNA sequencing analysis showed that HP P-C altered the composition of gut microbiota by raising the abundance of Lactobacillus and Akkermansia. In addition, metabolomics data identified seventeen main differential metabolites related to WIRS-induced gastric mucosal injury, primarily involving in tyrosine metabolism and betalain biosynthesis. HP P-C was found to regulate tyrosine metabolism and betalain biosynthesis by down-regulating the tyramine, L-tyrosine and L-dopa and up -regulating the gentisic acid and dopaquinone.

Conclusion: Taken together, this study indicated that HP P-C could effectively protect against WIRS-induced gastric mucosal lesions by modulating intestinal flora and metabolites.
Transcription factor ZEB1 coordinating with NuRD complex to promote oncogenesis through glycolysis in colorectal cancer
Authors: Gao Tianyang , Hao Xinhui , Zhang Jingyao , Huo Miaomiao , Hu Ting , Ma Tianyu , Yu Hefen , Teng Xu , Wang Yong , Yang Yunkai , Huang Wei , Wang Yan
Published: August 2024

Background

Colorectal cancer (CRC) is an aggressive primary intestinal malignancy with the third-highest incidence and second-highest mortality among all cancer types worldwide. Transcription factors (TFs) regulate cell development and differentiation owing to their ability to recognize specific DNA sequences upstream of genes. Numerous studies have demonstrated a strong correlation between TFs, the etiology of tumors, and therapeutic approaches. Here, we aimed to explore prognosis-related TFs and comprehend their carcinogenic mechanisms, thereby offering novel insights into the diagnosis and management of CRC.

Materials and Methods

Differentially expressed TFs between CRC and normal tissues were identified leveraging The Cancer Genome Atlas database, Weighted correlation network analysis and Cox regression analysis were performed to identify prognosis-related TFs. The cellular functions of hub TF zinc finger E-box binding homeobox 1 (ZEB1) were determined using by 5-ethynyl-2′-deoxyuridine and cell invasion assays in CRC cells. RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes enrichment, and gene set enrichment analyses were used to identify the cellular processes in which ZEB1 participates. Immunoaffinity purification, silver staining mass spectrometry, and a chromatin immunoprecipitation assay were conducted to search for proteins that might interact with ZEB1 and the target genes they jointly regulate.

Results

Thirteen central TFs related to prognosis were identified through bioinformatics analysis techniques. Among these TFs, ZEB1 emerged as the TF most closely associated with CRC, as determined through a combination of regulatory network diagrams, survival curves, and phenotype analyses. ZEB1 promotes CRC cell growth by recruiting the NuRD(MTA1) complex, and the ZEB1/NuRD(MTA1) complex transcriptionally represses glycolysis-associated tumor suppressor genes.

Conclusion

Our study not only identified a hub biomarker related to CRC prognosis but also revealed the specific molecular mechanisms through which ZEB1 affects cancer progression. These insights provide crucial evidence for the diagnosis of CRC and potential treatment opportunities.
Phytochemistry, pharmacological effects and mechanism of action of volatile oil from Panax ginseng C.A.Mey: a review
Authors: Xu Yanan , Bian Shuai , Shang LiYing , Wang Xin , Bai Xueyuan , Zhang Wei
Published: August 2024

Panax ginseng (P. ginseng), a traditional and highly valued botanical drug, has been used for thousands of years and is known around the world for its uses in food, medicine, and healthcare. The comprehensive study of P. ginseng is crucial for the quality assurance of medicinal materials and optimal resource utilization. Despite being present in trace amounts, P. ginseng volatile oil has a wide range of chemical metabolites with important medicinal potential. The volatile oil has shown promise in defending the cardiovascular system, as well as in terms of its ability of antibacterial, anti-aging, anti-platelet coagulation, anti-inflammatory, support the nervous system nutritionally, and shield it from harm. Due to its low composition and lack of thorough investigation, P. ginseng volatile oil’s therapeutic applicability is still restricted although it exhibited many benefits. This review aims to provide insights into the chemical composition, extraction processes, pharmacological effects, and mechanisms of action of P. ginseng volatile oil, and to provide theoretical support and guidelines for future research and clinical application.
Potentially inappropriate prescribing among older adults with hypertension in China: prevalence and related comorbidities across different outpatient settings
Authors: Chen Jiaqi , Wang Shuang , Lu Lvliang , Yang Yujie , Wang Kai , Zheng Jing , Zhou Zhijiang , Guo Pi , Cai Yunpeng , Zhang Qingying
Published: August 2024

Purpose

Potentially inappropriate prescribing (PIP) is commonly encountered in older adults; yet, there is limited information on the occurrence of PIP among older adults with hypertension. This study aims to determine and compare the prevalence of PIP and its association with comorbidities in older adult outpatients with hypertension across hospitals and community health centers (CHCs).

Methods

This 3-year (2015–2017) repeated cross-sectional study used electronic medical records from Shenzhen, China, involving 62 hospitals and 678 primary medical institutions. PIP was defined using the 2019 Beers Criteria. Older adults (≥65 years) with hypertension and at least one outpatient prescription were included. Modified Poisson regression analysis was used to assess the association between chronic comorbidities, healthcare settings, and PIP.

Results

The prevalence of PIP in old adult outpatients with hypertension in 2015, 2016, and 2017 was 46.32%, 46.98%, and 46.58% in hospitals, with a sample size of 38,411, 46,235, and 50,495, respectively, and 29.14%, 26.66%, and 29.84% in CHCs, with a sample size of 26,876, 29,434, and 34,775 respectively. The top four most popular PIP in hospitals and CHCs was proton-pump inhibitors (PPIs), diuretics, benzodiazepines, and non-cyclooxygenase-selective non-steroidal anti-inflammatory drugs (NSAIDs), respectively. PIP was most associated with chronic gastrointestinal disease (adjusted prevalence ratio = 1.54, 95% confidence interval [CI] = 1.50–1.59) and mental and behavioral disorders (adjusted prevalence ratio = 1.49, 95% CI = 1.46–1.53) in hospitals and with mental and behavioral disorders (adjusted prevalence ratio = 1.99; 95% CI = 1.95–2.03) and musculoskeletal system and connective tissue disorders (adjusted prevalence ratio = 1.33; 95% CI = 1.31–1.36) in CHCs. The prevalence of PIP was significantly higher in hospital settings than in CHCs (adjusted prevalence ratio = 1.65; 95% CI = 1.63–1.66).

Conclusion

Among older adult outpatients with hypertension in Shenzhen, PIP was more prevalent in hospitals than in CHCs. The comorbidities most strongly associated with PIP were chronic gastrointestinal disease and mental and behavioral disorders in hospitals and mental and behavioral disorders in CHCs. Clinical pharmacy integration needs to be considered to reduce inappropriate prescribing in this vulnerable population.